CN114767810B - Traditional Chinese medicine composition for treating acute lung injury as well as preparation method and application thereof - Google Patents

Abstract

The invention discloses a traditional Chinese medicine composition for treating acute lung injury, a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicine compound preparations. The invention relates to a traditional Chinese medicine composition for treating acute lung injury, which is prepared from the following raw materials in parts by weight: 5 to 20 parts of raw ephedra, 5 to 20 parts of cimicifuga foetida, 5 to 30 parts of angelica sinensis, 5 to 30 parts of rhizoma anemarrhenae, 5 to 40 parts of rhizoma polygonati officinalis, 5 to 30 parts of radix scutellariae, 5 to 30 parts of radix paeoniae alba, 5 to 40 parts of radix asparagi, 5 to 40 parts of sweet wormwood, 5 to 40 parts of turtle shell, 5 to 20 parts of fructus amomi, 5 to 30 parts of magnolia officinalis, 5 to 50 parts of gypsum, 5 to 40 parts of rhizoma atractylodis and 5 to 20 parts of liquorice. The invention prevents pathogenic bacteria from colonizing by regulating the structural distribution and composition of intestinal flora and by up-regulating the immune response of the organism. Improving the imbalance of intestinal flora, increasing beneficial flora capable of producing short chain fatty acid, inhibiting harmful flora, and regulating flora. Has obvious treatment effect on acute lung injury and has good clinical application prospect.

Description

Traditional Chinese medicine composition for treating acute lung injury as well as preparation method and application thereof

Technical Field

The invention belongs to the technical field of traditional Chinese medicine compound preparations, and in particular relates to a traditional Chinese medicine composition for treating acute lung injury, a preparation method and application thereof.

Background

Acute lung injury (Acute lung injury, ALI) is an acute, diffuse inflammatory lung injury caused by various internal and external lung pathogenic factors, which in turn causes a clinical syndrome of acute respiratory failure. ALI is one of the common respiratory critical diseases, and the death rate of the ALI is as high as 40% -50% in an intensive care unit.

ALI is essentially an uncontrolled inflammatory response, the pathogenesis of which is not yet fully elucidated, and currently there is still a lack of effective therapeutic strategies, with mortality rates still being high, only in terms of reducing bacterial load and reducing organ damage due to excessive inflammation. At present, various infectious diseases present a clear trend and powerful reburning process worldwide, the occurrence of drug resistance in the process is accompanied with antibiotic treatment, the process is inevitably high in certainty, a large number of antibiotics which are high-efficiency and stable in the past treatment suffer from the dilemma of sensitivity reduction and even treatment failure, and particularly the occurrence of 'superbacteria' in recent years, so that the traditional anti-infection treatment strategy and the drug development idea face significant challenges.

Disclosure of Invention

Aiming at the problem of immune lung injury caused by intestinal tract microbial flora imbalance of rats with acute lung injury caused by intestinal ischemia reperfusion, the invention provides a traditional Chinese medicine composition for treating acute lung injury and a preparation method and application thereof.

In order to achieve the above purpose, the present invention adopts the following technical scheme:

a traditional Chinese medicine composition for treating acute lung injury is prepared from the following raw materials in parts by weight: 5 to 20 parts of raw ephedra, 5 to 20 parts of cimicifuga foetida, 5 to 30 parts of angelica sinensis, 5 to 30 parts of rhizoma anemarrhenae, 5 to 40 parts of rhizoma polygonati officinalis, 5 to 30 parts of radix scutellariae, 5 to 30 parts of radix paeoniae alba, 5 to 40 parts of radix asparagi, 5 to 40 parts of sweet wormwood, 5 to 40 parts of turtle shell, 5 to 20 parts of fructus amomi, 5 to 30 parts of magnolia officinalis, 5 to 50 parts of gypsum, 5 to 40 parts of rhizoma atractylodis and 5 to 20 parts of liquorice.

Further, the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 5 to 10 parts of raw ephedra, 5 to 10 parts of cimicifuga foetida, 5 to 30 parts of angelica sinensis, 5 to 20 parts of rhizoma anemarrhenae, 5 to 40 parts of rhizoma polygonati officinalis, 5 to 30 parts of radix scutellariae, 5 to 30 parts of radix paeoniae alba, 5 to 40 parts of radix asparagi, 5 to 40 parts of sweet wormwood, 5 to 40 parts of turtle shell, 5 to 20 parts of fructus amomi, 5 to 30 parts of magnolia officinalis, 5 to 50 parts of gypsum, 5 to 40 parts of rhizoma atractylodis and 5 to 20 parts of liquorice.

Further, the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 10 parts of raw ephedra, 10 parts of cimicifuga foetida, 15 parts of Chinese angelica, 15 parts of rhizoma anemarrhenae, 30 parts of rhizoma polygonati officinalis, 15 parts of radix scutellariae, 15 parts of radix paeoniae alba, 30 parts of radix asparagi, 30 parts of sweet wormwood herb, 30 parts of turtle shell, 10 parts of fructus tsaoko, 15 parts of magnolia officinalis, 30 parts of gypsum, 30 parts of rhizoma atractylodis and 10 parts of liquorice.

A preparation method of a traditional Chinese medicine composition for treating acute lung injury comprises the steps of taking the required weight parts of raw ephedra herb, cimicifuga foetida, chinese angelica, rhizoma anemarrhenae, radix polygonati officinalis, radix scutellariae, white paeony root, radix asparagi, sweet wormwood herb, turtle shell, tsaoko cardamom, magnolia officinalis, gypsum, rhizoma atractylodis and liquorice, crushing into fine powder, mixing and soaking for 30min, decocting for 2 times, mixing the two decocted filtered substances, and concentrating to a final concentration of 2g/mL.

Application of the traditional Chinese medicine composition in preparing medicines for treating acute lung injury is provided.

Further, the pharmaceutical dosage forms of the Chinese medicinal composition include liquid dosage forms, solid dosage forms, semi-solid dosage forms and gaseous dosage forms.

Further, the liquid dosage form comprises: aromatic water, solution, injection, mixture, lotion and paint; the solid dosage forms comprise powder, pills, tablets, films, capsules and granules; the semi-solid dosage form comprises: ointments, pastes, gels; the gas dosage form comprises: aerosol and spray.

Compared with the prior art, the invention has the following advantages:

the traditional Chinese medicine composition disclosed by the invention can effectively relieve lung injury caused by intestinal ischemia reperfusion, inhibit the expansion of pulmonary small arterial lumen and thrombosis, protect the pulmonary alveolus and bronchiole tissue structures, and maintain the normal structures of intestinal mucosa myometrium and serous membrane. The invention prevents pathogenic bacteria from colonizing by regulating the structural distribution and composition of intestinal flora and by up-regulating the immune response of the organism. Improving the imbalance of intestinal flora, increasing beneficial flora capable of producing short chain fatty acid, inhibiting harmful flora, and regulating flora. Has obvious treatment effect on acute lung injury and has good clinical application prospect.

Drawings

FIG. 1 is a graph showing changes in W/D of intestinal ischemia reperfusion lung injury;

FIG. 2 is a diagram of the pathomorphology of intestinal ischemia reperfusion lung injury;

FIG. 3 is a graph of TLR4, my D88, TRAF6 protein expression;

FIG. 4 is a species classification diagram of Illumina sequencing results;

FIG. 5 is a graph of intestinal flora composition change (portal level relative abundance) in rats with intestinal ischemia reperfusion lung injury;

FIG. 6 is a graph of intestinal flora composition change (relative abundance at the genus level) in rats with intestinal ischemia reperfusion lung injury;

FIG. 7 is a heat map of intestinal flora species;

FIG. 8 is a graph of the relative amounts of differential metabolites in rat serum.

Detailed Description

The invention is further described below with reference to the drawings and specific examples.

Example 1

The embodiment provides a traditional Chinese medicine composition, which comprises the following raw material medicines: 10g of raw ephedra herb, 10g of cimicifuga rhizome, 15g of Chinese angelica, 15g of rhizoma anemarrhenae, 30g of rhizoma polygonati officinalis, 15g of baical skullcap root, 15g of white paeony root, 30g of radix asparagi, 30g of sweet wormwood herb, 30g of turtle shell, 10g of tsaoko cardamon, 15g of officinal magnolia bark, 30g of gypsum, 30g of rhizoma atractylodis and 10g of liquorice.

Pulverizing the above materials into fine powder, mixing, soaking for 30min, decocting for 2 times, mixing the two decoctions, and concentrating to a final concentration of 2g/mL. The aromatic water agent is prepared by a conventional method.

Example 2

14g of raw ephedra, 8g of cimicifuga foetida, 10g of Chinese angelica, 20g of rhizoma anemarrhenae, 35g of rhizoma polygonati officinalis, 25g of radix scutellariae, 10g of radix paeoniae alba, 8g of radix asparagi, 26g of sweet wormwood, 14g of turtle shell, 18g of fructus tsaoko, 24g of magnolia officinalis, 12g of gypsum, 22g of rhizoma atractylodis and 15g of liquorice.

Pulverizing the above materials into fine powder, mixing, soaking for 30min, decocting for 2 times, mixing the two decoctions, and concentrating to a final concentration of 2g/mL. Making into powder by conventional method.

Example 3

18g of raw ephedra, 12g of cimicifuga foetida, 24g of Chinese angelica, 14g of rhizoma anemarrhenae, 15g of rhizoma polygonati officinalis, 15g of radix scutellariae, 12g of white paeony root, 36g of radix asparagi, 26g of sweet wormwood herb, 30g of turtle shell, 15g of fructus tsaoko, 18g of magnolia officinalis, 8g of gypsum, 8g of rhizoma atractylodis and 8g of liquorice.

Pulverizing the above materials into fine powder, mixing, soaking for 30min, decocting for 2 times, mixing the two decoctions, and concentrating to a final concentration of 2g/mL. Making into ointment by conventional method.

Example 4

18g of raw ephedra, 18g of cimicifuga foetida, 20g of Chinese angelica, 8g of rhizoma anemarrhenae, 15g of rhizoma polygonati officinalis, 15g of radix scutellariae, 12g of white paeony root, 12g of radix asparagi, 20g of sweet wormwood herb, 5g of turtle shell, 20g of fructus tsaoko, 30g of magnolia officinalis, 35g of gypsum, 35g of rhizoma atractylodis and 15g of liquorice.

Pulverizing the above materials into fine powder, mixing, soaking for 30min, decocting for 2 times, mixing the two decoctions, and concentrating to a final concentration of 2g/mL. Making into aerosol by conventional method.

Example 5

8g of raw ephedra, 15g of cimicifuga foetida, 5g of Chinese angelica, 12g of rhizoma anemarrhenae, 25g of rhizoma polygonati officinalis, 25g of radix scutellariae, 20g of white paeony root, 20g of radix asparagi, 25g of sweet wormwood herb, 25g of turtle shell, 10g of tsaoko cardamon, 15g of magnolia officinalis, 25g of gypsum, 15g of rhizoma atractylodis and 10g of liquorice.

Pulverizing the above materials into fine powder, mixing, soaking for 30min, decocting for 2 times, mixing the two decoctions, and concentrating to a final concentration of 2g/mL. Making into solution by conventional method.

Example 6

5g of raw ephedra herb, 5g of cimicifuga rhizome, 5g of Chinese angelica, 5g of rhizoma anemarrhenae, 5g of rhizoma polygonati officinalis, 5g of baical skullcap root, 5g of white paeony root, 5g of radix asparagi, 5g of sweet wormwood herb, 5g of turtle shell, 5g of tsaoko cardamon, 5g of officinal magnolia bark, 5g of gypsum, 5g of rhizoma atractylodis and 5g of liquorice.

Pulverizing the above materials into fine powder, mixing, soaking for 30min, decocting for 2 times, mixing the two decoctions, and concentrating to a final concentration of 2g/mL. Making into pill by conventional method.

Example 7

6g of raw ephedra, 12g of cimicifuga foetida, 12g of Chinese angelica, 6g of rhizoma anemarrhenae, 6g of rhizoma polygonati officinalis, 24g of radix scutellariae, 24g of radix paeoniae alba, 36g of radix asparagi, 36g of sweet wormwood, 12g of turtle shell, 16g of fructus tsaoko, 24g of magnolia officinalis, 48g of gypsum, 6g of rhizoma atractylodis and 12g of liquorice.

Pulverizing the above materials into fine powder, mixing, soaking for 30min, decocting for 2 times, mixing the two decoctions, and concentrating to a final concentration of 2g/mL. Making into spray by conventional method.

Example 8

12g of raw ephedra, 12g of cimicifuga foetida, 22g of Chinese angelica, 16g of rhizoma anemarrhenae, 32g of rhizoma polygonati officinalis, 16g of radix scutellariae, 16g of radix paeoniae alba, 16g of radix asparagi, 22g of sweet wormwood, 8g of turtle shell, 16g of fructus tsaoko, 16g of magnolia officinalis, 32g of gypsum, 32g of rhizoma atractylodis and 12g of liquorice.

Pulverizing the above materials into fine powder, mixing, soaking for 30min, decocting for 2 times, mixing the two decoctions, and concentrating to a final concentration of 2g/mL. Making into injection by conventional method.

Example 9

10g of raw ephedra, 10g of cimicifuga foetida, 30g of Chinese angelica, 20g of rhizoma anemarrhenae, 40g of rhizoma polygonati officinalis, 30g of radix scutellariae, 30g of radix paeoniae alba, 40g of radix asparagi, 40g of sweet wormwood herb, 40g of turtle shell, 20g of fructus amomi, 30g of magnolia officinalis, 50g of gypsum, 40g of rhizoma atractylodis and 20g of liquorice.

Pulverizing the above materials into fine powder, mixing, soaking for 30min, decocting for 2 times, mixing the two decoctions, and concentrating to a final concentration of 2g/mL. Making into capsule by conventional method.

Example 10

20g of raw ephedra, 20g of cimicifuga foetida, 30g of Chinese angelica, 30g of rhizoma anemarrhenae, 40g of rhizoma polygonati officinalis, 30g of radix scutellariae, 30g of radix paeoniae alba, 40g of radix asparagi, 40g of sweet wormwood herb, 40g of turtle shell, 20g of fructus amomi, 30g of magnolia officinalis, 50g of gypsum, 40g of rhizoma atractylodis and 20g of liquorice.

Pulverizing the above materials into fine powder, mixing, soaking for 30min, decocting for 2 times, mixing the two decoctions, and concentrating to a final concentration of 2g/mL. Making into gel by conventional method.

Example 11

1. Influence of the composition on the pathological damage of the tissue of rats with acute lung injury induced by ischemia reperfusion of the intestines

(1) Animals, medicines and instruments: wistar male rats 24, purchased from beijing vernalia laboratory animal technologies limited, license number: SCXK 2016-0006, weight of 180 g-220 g. And approved by the laboratory animal ethics committee of the university of shanxi traditional Chinese medicine.

(2) Experimental instrument: noninvasive arterial clamp (Beijing Ji Nuo Takara Shuzo Co., ltd.), fecal DNA extraction kit (OMEGA-R6828, U.S. OMEGA Bio-Tek Co., ltd.), low-speed centrifuge (KDC-1044, KDC-KC Co., ltd.), ACQUITY UPLC BEH C chromatographic column (AT. PEG-20M, department of chemical and physical research, orchis, china), high performance liquid chromatograph (Siemens Feisha science Co., ultiMate 3000), four-pole-electrostatic field orbitrap high-resolution mass spectrometer (Siemens Feisha science Co., UHPLC-Q-Exactive Orbitrap-MS).

(3) Animal model establishment and dosing: rats were randomly divided into 3 groups: sham, model (ALI), example 1 (example 1) (28 g kg) ^-1 ). Before molding, sham and ALI were administered with distilled water, and example 1 was performed by pouring the water decoction of example 1 into the stomach, and administration was continued for 3 days.

Injecting 10% chloral hydrate into abdominal cavity at 0.2mL/100gb.w., fixing in supine position, sterilizing with alcohol, taking about 3cm of abdominal median incision into abdominal cavity, pulling intestinal canal to right to outside, wetting gauze soaked with 0.9% physiological saline to expose intestinal canal, exposing and freeing superior mesenteric artery (superior mesenteric artery, SMA), clamping SMA with non-invasive arterial clamp to cause small intestine complete ischemia, and then returning small intestine to abdominal cavity, and closing abdominal operation incision. After 1h of continuous ischemia, the non-invasive arterial clamp is removed, the tissue is restored to blood supply for 2h, and the experiment is ended. The sham group only had free SMA and did not clamp.

(4) Animal treatment and sample retention: the right lung is separated, the upper right lung is taken, the external lung tissue is carefully removed, physiological saline is used for rinsing, filter paper is used for sucking the surface liquid of the lung, the lung is immediately placed on an electronic balance to weigh the lung, and then the lung is placed in a 60 ℃ oven to be dried for 48 hours until the weight is constant, and the (W/D) ratio is calculated. The lung tissue and the distal colon were harvested on ice, washed with ice saline, fixed with 4% paraformaldehyde, paraffin-embedded and HE stained in sections. The conditions of intrapulmonary hemorrhage, intrapulmonary inflammatory exudation, neutrophil infiltration, alveolar wall thickening degree, pulmonary hyaline membrane formation, etc. were observed and quantified as integral (PI) of 0-4. Animal manure is collected, and a high-throughput sequencing method is utilized to analyze the genome of the sample intestinal microorganism bacteria.

The right lung is separated, the upper right lung is taken, the external lung tissue is carefully removed, physiological saline is used for rinsing, filter paper is used for sucking the surface liquid of the lung, the lung is immediately placed on an electronic balance to weigh the lung, and then the lung is placed in a 60 ℃ oven to be dried for 48 hours until the weight is constant, and the (W/D) ratio is calculated.

(5) Example 1 effect on lung tissue wet/dry weight ratio (as shown in fig. 1, which is a graph of W/D change in intestinal ischemia reperfusion lung injury): the ALI group W/D increased (P < 0.01) compared to Sham group, while example 1 significantly decreased (P < 0.01) in dry prognosis, suggesting that example 1 may be effective in alleviating lung injury caused by ischemia reperfusion of the intestine.

(6) Example 1 effects on lung histopathology (as shown in fig. 2, a pathomorphology diagram of intestinal ischemia reperfusion lung injury): HE staining of rat lung, distal colon tissue found that extensive lung tissue necrosis was seen in ALI group; example 1 group arteriolar lumen dilation, thrombosis, alveolar and bronchioles were not abnormal.

The pathological results of the far-end colon tissues show that the ALI group small intestine mucous membrane, submucosa, myolayer necrosis, inflammatory cell infiltration and fat necrosis are extensive; example 1 group mucosa was not significantly altered, submucosal vasodilation, congestion, interstitial loose edema, and normal myometrial and serosal structures were seen.

(7) Example 1 effect on TLR4, my D88, TRAF6 protein expression levels (as shown in fig. 3, fig. 3 is a graph of TLR4, my D88, TRAF6 protein expression (a: sham; B: ALI; C: QYF)): the levels of TLR4, myD88, TRAF6 expression in rat lung tissue of ALI group were significantly increased compared to Sham group, whereas TLR4, my D88, TRAF6 expression in rat lung tissue was shown to be reduced to a different extent (P < 0.05) after administration of the treatment of example 1.

2. Example 1 action mechanism for inhibiting acute Lung injury caused by ischemia reperfusion of intestine by intestinal flora modulation

Two-way conversations driven by the metabolic state of the microbiota are critical to maintaining the health and homeostasis of an individual host, while dysregulation of these dynamics is a key driver for many diseases, so studies on the metabolic pathways of the microbiota may provide a new strategy for the treatment of ALI. Studies have shown that dysregulation of intestinal flora affects pulmonary diseases via the intestinal-pulmonary axis. Dysbacteriosis in the gut may increase the risk of flora translocation by disrupting the integrity of the gut barrier. If the flora leaving the intestine migrates to the lungs, it activates the immune system of the lungs, thereby exacerbating the immune damage to the lungs.

(1) Animal experiments and sequencing analysis of acute lung injury caused by intestinal ischemia reperfusion: constructing an acute lung injury model, grouping, feeding medicine, and killing, and taking serum and colon tissues as before. Reference NEBUltra ^TM DNA Library Prep Kit for/>Extracting rat feces, genome DNA, PCR amplification and purification, and constructing a library of samples with qualified quality. The intestinal microbial genome of the sample was sequenced using an Illumina HiSeq high throughput sequencing platform.

(2) Example 1 effect on species classification and intestinal microbiota composition: comparing each sample clear Reads with non-redundant gene sets using Bowtie2, obtaining abundance of each gene in the sample using Samtools, we can obtain relative abundance of flora at the level of Kingdom, phylum (phyllum), class (Class), order (Order), family, genus (Genus), species (specie) (relative abundance); alpha diversity calculation, beta diversity analysis, comparison of differences in relative abundance of the group of bacteria, heat map analysis and differential species screening are performed on species in the sample.

And (3) carrying out protein sequence alignment on the gene protein sequence and the NCBI-Nr database by using DIAMOND software to obtain species classification annotation information. Comparing the sequencing sequences of the samples at the species level, and finding that (as shown in a species classification chart of the Illumina sequencing result in FIG. 4 (K: kingdom; P: phylum; C: class; O: order; F: family; G: genus; S: species)), the phylum Firmicutes and the phylum bacteroides (bacteroides) are dominant at the phylum level; the order level, clostridia (Clostridia), lactobacillus (Lactobacillus) under Firmics; the bacteroidae (Bacteroidaceae) and the Prevotellaceae (Prevolvulaceae) are high in abundance.

The composition of the intestinal microorganisms of the rats after the acute lung injury caused by the intestinal ischemia reperfusion is obviously different from that of the sham operation group in portal and genus level (as shown in fig. 5 and 6, fig. 5 is a graph of intestinal flora composition change (portal level relative abundance) of the rats with the intestinal ischemia reperfusion lung injury, and fig. 6 is a graph of intestinal flora composition change (genus level relative abundance) of the rats with the intestinal ischemia reperfusion lung injury). Intestinal ischemia reperfusion results in a change in intestinal microbiota composition, overall reduced species diversity, and the extent of intestinal dysfunction is positively correlated with the extent of lung injury and is critical for microbiota changes. Whereas example 1 shows an increase in the number of rats with intestinal firmicutes, a decrease in the number of bacteroidetes, and an increase in the ratio of firmicutes to bacteroidetes; the relative decrease in Prevotella, the relative increase in Lactobacillus and bifidobacterium, and the increase in Clostridium, example 1 restored to some extent the intestinal microbial diversity of ALI rats.

The firmicutes can produce SCFAs which are directly utilized by organisms and are mainly used for producing butyrate bacteria. Lactobacillus as a probiotic can prevent airway inflammation caused by respiratory syncytial virus infection, and clostridium can enhance resistance to pulmonary infection by Nod2 and GM-CSF. Prevolella species have a recognized pathogenicity for pulmonary infection and can promote viral infection and induce IL-6 production. Clostridium is a butyrate-producing intestinal probiotic that inhibits the growth of harmful gastrointestinal bacteria. The acute lung injury group has the advantages that the thick-walled bacteria and the bacteroides are reduced, the bacteroides, the Prevotella and the lactic acid bacteria are relatively reduced, the Shannon index is reduced, and the Simpson index is increased, so that the acute lung injury group after the intestinal ischemia reperfusion treatment has reduced relative flora diversity. While example 1 can restore the diversity of intestinal flora to a certain extent, example 1 can prevent colonization of pathogenic bacteria by adjusting the structural distribution and composition of intestinal flora and by up-regulating immune response of organism. The flora structure composition in the samples of the Sham group and the example 1 group was further found to be more similar in cluster tree and PCoA analysis. Example 1 can improve the imbalance of intestinal flora to a certain extent, increase beneficial flora capable of producing short chain fatty acid, inhibit harmful flora, and play a positive role in regulating flora.

Species thermogram analysis was performed based on the species composition and relative abundance of each sample (as shown in fig. 7). Selecting the genus of 20 before abundance, and carrying out cluster analysis by using R language. As can be seen from the figure, the samples of the sham group after the drug treatment of example 1 were closer in distance, higher in similarity of microorganism composition and abundance, and separated from the samples of the model group.

(3) And (5) comparing the species annotation information with the functional annotation information, the functions and the abundance of the species of the genes by utilizing a KEGG, GO, COG database and the like. From the results of KEGG functional annotation, the intestinal flora function of acute lung injury rats is closely related to the deregulation of basic metabolic pathways Carbohydrate metabolism, amino acid metabolism, energy metabolism, nucleotide metabolism, catalytic activity and metabolic process. The intestinal microbiota has metabolic activity such as streptococcus pentosus, which can increase antioxidant activity of fermented milk, and can produce SCFAs, and anaerobic microorganisms in colon such as Bacteroides, roche and Bifidobacterium, which can ferment indigestible carbohydrate, and has positive effect on intestinal epithelial cell differentiation and proliferation. COG databases indicate that alterations in intestinal microbiota may ameliorate symptoms of acute lung injury through metabolic pathways. Example 1 the treatment group promoted basal metabolism (including Carbohydrate transport and metabolism, amino acid transport and metabolism) and the improvement in acute lung injury rats treated in example 1 was closely related to these metabolic pathways.

Intestinal microorganisms can also affect the host immune system by cytokine signaling. The symbiotic microbiota stimulates TLR4 signaling, activating the transcription factor kappa light chain enhancer of activated B cells (NF- κb) via myeloid differentiation primary response protein (MyD 88) to induce pro-inflammatory gene expression. The host's innate immune system (i.e., TLR4, 2, 5 receptors and NLRP 3) affects the composition of the microbiota, while intestinal inflammation and immune activation secondary to dysbacteriosis or dysfunction of the intestinal barrier may also further lead to intestinal, systemic immune inflammatory responses through a variety of potential mechanisms. Microbial-derived stimuli are key mediators of inflammatory response involved in gut-lung signal communication. Intestinal microbiota through its structural components and metabolites, limit translocation of microbiota from the intestinal lumen to the circulatory system, preventing systemic immune responses. Intestinal microbiota acts as a trigger for TLR4 signaling, inducing TLR signaling during small intestine ischemia, further activating a complex signaling cascade, recruiting the adapter molecule MyD 88), causing acute intestinal, lung, inflammatory and endothelial injury. TRAF6 is a downstream signal of the TLR/IL-1R superfamily, further regulating immune responses.

(4) Example 1 effect on metabolism (as shown in figure 8, schematic representation of the relative amounts of differential metabolites in rat serum): metabolic profiling was performed on rat serum samples using a UHPLC-Q-Exactive Orbitrap-MS based method followed by multivariate analysis to determine key biomarkers, resulting in 19 potential signature metabolites after ALI group and example 1 treatment. Metabolites such as choline metabolite Trimethylamine (TMA), secondary BA, deoxycholic acid (DCA) and SCFA in the host cannot be produced without bacterial fermentation. Ether lipids regulate cell differentiation, affect cell signaling, and plasmalogens have protective effects on oxidative damage by reducing oxidative stress as a potential endogenous antioxidant. Pan released by intestinal microbiome is a limiting precursor of intracellular CoA synthesis, and in many chronic inflammatory diseases Pan and cysteamine have good regulation effect on sustained metabolism, oxidation or hypoxia stress of tissues, limiting ROS-induced cell damage. Example 1 it is possible to exert anti-inflammatory, immunomodulatory effects by downregulating Platelet-activating factor, upregulating d-pantothenic acid, affecting ether lipid metabolism and pantothenate and coenzyme a metabolic pathways.

Example 12

The experiment of example 11 was carried out by substituting examples 2 to 10 for example 1, and the effects of effectively reducing the lung injury caused by intestinal ischemia reperfusion, inhibiting the expansion of pulmonary small arterial lumen and thrombosis, protecting the pulmonary alveolus and bronchiolar tissue structures, and maintaining the normal structures of intestinal mucosa myolayer and serosa were also achieved.

In conclusion, the invention prevents pathogenic bacteria from colonizing by regulating the structural distribution and composition of intestinal flora and by up-regulating the immune response of the organism. Improving the imbalance of intestinal flora, increasing beneficial flora capable of producing short chain fatty acid, inhibiting harmful flora, and regulating flora. Has obvious treatment effect on acute lung injury and has good clinical application prospect.

What is not described in detail in the present specification belongs to the prior art known to those skilled in the art. While the foregoing describes illustrative embodiments of the present invention to facilitate an understanding of the present invention by those skilled in the art, it should be understood that the present invention is not limited to the scope of the embodiments, but is to be construed as protected by the accompanying claims insofar as various changes are within the spirit and scope of the present invention as defined and defined by the appended claims.

Claims (6)

1. A traditional Chinese medicine composition for treating acute lung injury is characterized in that: the traditional Chinese medicine is prepared from the following raw materials in parts by weight: 5-20 parts of raw ephedra, 5-20 parts of cimicifuga foetida, 5-30 parts of angelica sinensis, 5-30 parts of rhizoma anemarrhenae, 5-40 parts of rhizoma polygonati officinalis, 5-30 parts of radix scutellariae, 5-30 parts of radix paeoniae alba, 5-40 parts of radix asparagi, 5-40 parts of sweet wormwood, 5-40 parts of turtle shell, 5-20 parts of fructus amomi, 5-30 parts of magnolia officinalis, 5-50 parts of gypsum, 5-40 parts of rhizoma atractylodis and 5-20 parts of liquorice;

the preparation method of the traditional Chinese medicine composition comprises the following steps: pulverizing herba Ephedrae, cimicifugae rhizoma, radix Angelicae sinensis, rhizoma anemarrhenae, rhizoma Polygonati Odorati, scutellariae radix, radix Paeoniae alba, radix asparagi, herba Artemisiae Annuae, carapax Trionycis, fructus Tsaoko, cortex Magnolia officinalis, gypsum Fibrosum, rhizoma Atractylodis and Glycyrrhrizae radix into fine powder, mixing, soaking for 30min, decocting for 2 times, mixing the two decoctions, and concentrating to a final concentration of 2g/mL.

2. The traditional Chinese medicine composition for treating acute lung injury according to claim 1, wherein the traditional Chinese medicine composition is characterized in that: the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 5-10 parts of raw ephedra, 5-10 parts of cimicifuga foetida, 5-30 parts of angelica sinensis, 5-20 parts of rhizoma anemarrhenae, 5-40 parts of rhizoma polygonati officinalis, 5-30 parts of radix scutellariae, 5-30 parts of radix paeoniae alba, 5-40 parts of radix asparagi, 5-40 parts of sweet wormwood, 5-40 parts of turtle shell, 5-20 parts of fructus amomi, 5-30 parts of magnolia officinalis, 5-50 parts of gypsum, 5-40 parts of rhizoma atractylodis and 5-20 parts of liquorice.

3. The traditional Chinese medicine composition for treating acute lung injury according to claim 1, wherein the traditional Chinese medicine composition is characterized in that: the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 10 parts of raw ephedra, 10 parts of cimicifuga foetida, 15 parts of Chinese angelica, 15 parts of rhizoma anemarrhenae, 30 parts of rhizoma polygonati officinalis, 15 parts of radix scutellariae, 15 parts of radix paeoniae alba, 30 parts of radix asparagi, 30 parts of sweet wormwood herb, 30 parts of turtle shell, 10 parts of fructus tsaoko, 15 parts of magnolia officinalis, 30 parts of gypsum, 30 parts of rhizoma atractylodis and 10 parts of liquorice.

4. Use of the traditional Chinese medicine composition according to any one of claims 1-3 in preparing a medicament for treating acute lung injury.

5. The use of the traditional Chinese medicine composition according to claim 4 in preparing a medicament for treating acute lung injury: the method is characterized in that: the pharmaceutical dosage forms of the traditional Chinese medicine composition comprise liquid dosage forms, solid dosage forms, semi-solid dosage forms and gas dosage forms.

6. The use of the traditional Chinese medicine composition according to claim 5 in preparing a medicament for treating acute lung injury: the method is characterized in that: the liquid dosage form comprises: injection, mixture, lotion, and liniment; the solid dosage forms comprise powder, pills, tablets, films, capsules and granules; the semi-solid dosage form comprises: ointments, pastes, gels; the gas dosage form comprises: aerosol and spray.