CN114767810A - Traditional Chinese medicine composition for treating acute lung injury and preparation method and application thereof - Google Patents

Traditional Chinese medicine composition for treating acute lung injury and preparation method and application thereof Download PDF

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CN114767810A
CN114767810A CN202210287485.1A CN202210287485A CN114767810A CN 114767810 A CN114767810 A CN 114767810A CN 202210287485 A CN202210287485 A CN 202210287485A CN 114767810 A CN114767810 A CN 114767810A
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lung injury
chinese medicine
traditional chinese
acute lung
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CN114767810B (en
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彭涛
马艳苗
樊慧杰
张育敏
陈富丽
宋博
刘明燃
赵丽君
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Shanxi University of Chinese Mediciine
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Abstract

The invention discloses a traditional Chinese medicine composition for treating acute lung injury as well as a preparation method and application thereof, belonging to the technical field of traditional Chinese medicine compound preparations. The traditional Chinese medicine composition for treating acute lung injury is prepared from the following raw material medicines 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 polygonatum, 5-30 parts of scutellaria baicalensis, 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 amomum tsao-ko, 5-30 parts of mangnolia officinalis, 5-50 parts of gypsum, 5-40 parts of rhizoma atractylodis and 5-20 parts of liquorice. The invention prevents pathogenic bacteria from colonizing by adjusting the structural distribution and composition of intestinal flora and by up-regulating the immune response of organisms. Improve the imbalance of intestinal flora, increase beneficial flora capable of producing short-chain fatty acid, inhibit harmful flora, and regulate flora. Has obvious treatment effect on acute lung injury and good clinical application prospect.

Description

Traditional Chinese medicine composition for treating acute lung injury and preparation method and application thereof
Technical Field
The invention belongs to the technical field of traditional Chinese medicine compound preparations, and particularly relates to a traditional Chinese medicine composition for treating acute lung injury, and a preparation method and application thereof.
Background
Acute Lung Injury (ALI) is a clinical syndrome of Acute and diffuse inflammatory lung injury caused by various internal and external pathogenic factors of the lung, which in turn causes Acute respiratory failure. ALI is one of the common respiratory critical diseases, and the fatality rate of ALI is up to 40-50% in an intensive care unit.
The nature of ALI is uncontrolled inflammatory reaction, the pathogenesis of ALI is not fully elucidated, and effective treatment methods are still lacking, and the mortality rate of the treatment strategy is still high only in terms of reducing bacterial load and organ damage caused by excessive inflammation. At present, various infectious diseases present a clear and powerful reignition process worldwide, the occurrence of drug resistance in the process is associated with antibiotic treatment, inevitable and highly inevitable, and a large number of antibiotics with high efficiency and stability in the prior treatment suffer from the difficulties of sensitivity reduction and even treatment failure, especially the occurrence of 'super bacteria' in recent years, so that the traditional anti-infection treatment strategy and the drug research and development concept face significant challenges.
Disclosure of Invention
The invention provides a traditional Chinese medicine composition for treating acute lung injury, a preparation method and application, aiming at the problem that the dyscrasia of intestinal microflora of rats with acute lung injury caused by intestinal ischemia reperfusion causes immune lung injury.
In order to achieve the purpose, the invention adopts the following technical scheme:
a traditional Chinese medicine composition for treating acute lung injury is prepared from the following raw material medicines 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 polygonatum, 5-30 parts of scutellaria baicalensis, 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 amomum tsao-ko, 5-30 parts of mangnolia officinalis, 5-50 parts of gypsum, 5-40 parts of rhizoma atractylodis and 5-20 parts of liquorice.
Further, the traditional Chinese medicine composition is prepared from the following raw medicines 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 polygonatum, 5-30 parts of scutellaria baicalensis, 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 amomum tsao-ko, 5-30 parts of mangnolia officinalis, 5-50 parts of gypsum, 5-40 parts of rhizoma atractylodis and 5-20 parts of liquorice.
Further, the traditional Chinese medicine composition is prepared from the following raw medicines in parts by weight: 10 parts of raw ephedra herb, 10 parts of skunk bugbane rhizome, 15 parts of Chinese angelica, 15 parts of common anemarrhena rhizome, 30 parts of fragrant solomonseal rhizome, 15 parts of baical skullcap root, 15 parts of white paeony root, 30 parts of cochinchnese asparagus root, 30 parts of sweet wormwood herb, 30 parts of turtle shell, 10 parts of tsaoko cardamon, 15 parts of officinal magnolia bark, 30 parts of raw gypsum, 30 parts of swordlike atractylodes rhizome and 10 parts of liquoric root.
A preparation method of a traditional Chinese medicine composition for treating acute lung injury comprises the steps of taking raw ephedra herb, cimicifuga foetida, angelica sinensis, rhizoma anemarrhenae, polygonatum odoratum, scutellaria baicalensis, radix paeoniae alba, asparagus, sweet wormwood, turtle shell, amomum tsao-ko, mangnolia officinalis, gypsum, rhizoma atractylodis and liquorice in required weight parts, crushing into fine powder, mixing, soaking for 30min, decocting for 2 times, mixing filtrates after two times of decoction, and concentrating to a final concentration of 2 g/mL.
An application of the above Chinese medicinal composition in preparing medicine for treating acute lung injury is provided.
Further, the pharmaceutical dosage forms of the traditional Chinese medicine composition comprise liquid dosage forms, solid dosage forms, semisolid dosage forms and gas dosage forms.
Further, the liquid dosage form comprises: aromatic water, solution, injection, mixture, lotion, and liniment; the solid dosage forms comprise powder, pill, tablet, pellicle, capsule, and granule; the semi-solid dosage form comprises: ointments, pastes, gels; the gaseous dosage form comprises: aerosol and spray.
Compared with the prior art, the invention has the following advantages:
the traditional Chinese medicine composition can effectively relieve lung injury caused by intestinal ischemia reperfusion, inhibit pulmonary arteriole lumen dilatation and thrombosis, protect alveolus and bronchiole tissue structures, and maintain normal structures of intestinal mucosa muscularis and serosa. The invention prevents pathogenic bacteria from colonizing by adjusting the structural distribution and composition of intestinal flora and by up-regulating the immune response of organisms. Improve the imbalance of intestinal flora, increase beneficial flora capable of producing short-chain fatty acid, inhibit harmful flora, and regulate flora. Has obvious treatment effect on acute lung injury and good clinical application prospect.
Drawings
FIG. 1 is a graph of W/D changes in intestinal ischemia-reperfusion lung injury;
FIG. 2 is a pathomorphogram of an intestinal ischemia-reperfusion lung injury;
FIG. 3 is the expression diagram of TLR4, My D88 and TRAF6 proteins;
fig. 4 is a species classification chart of Illumina sequencing results;
FIG. 5 is a graph of the alteration (portal level relative abundance) of intestinal microbiota composition in rats with intestinal ischemia-reperfusion lung injury;
FIG. 6 is a graph showing changes in the composition of intestinal flora (genus level relative abundance) in rats with ischemia-reperfusion lung injury;
FIG. 7 is a heat map of gut flora species;
FIG. 8 is a graph showing the relative content of different metabolites in rat serum.
Detailed Description
The invention is further described below with reference to the figures and the specific examples.
Example 1
The embodiment provides a traditional Chinese medicine composition, which comprises the following raw material medicines: 10g of raw ephedra, 10g of rhizoma cimicifugae, 15g of angelica sinensis, 15g of rhizoma anemarrhenae, 30g of radix polygonati officinalis, 15g of scutellaria baicalensis, 15g of radix paeoniae alba, 30g of radix asparagi, 30g of sweet wormwood, 30g of turtle shell, 10g of amomum tsao-ko, 15g of mangnolia officinalis, 30g of gypsum, 30g of rhizoma atractylodis and 10g of liquorice.
Pulverizing the above raw materials into fine powder, mixing, soaking for 30min, decocting for 2 times, mixing the filtrates after two times of decoction, and concentrating to final concentration of 2 g/mL. Preparing into aromatic water by conventional method.
Example 2
14g of raw ephedra herb, 8g of cimicifuga foetida, 10g of angelica, 20g of rhizoma anemarrhenae, 35g of polygonatum odoratum, 25g of scutellaria baicalensis, 10g of radix paeoniae alba, 8g of radix asparagi, 26g of sweet wormwood, 14g of turtle shell, 18g of amomum tsao-ko, 24g of magnolia officinalis, 12g of gypsum, 22g of rhizoma atractylodis and 15g of liquorice.
Pulverizing the above raw materials into fine powder, mixing, soaking for 30min, decocting for 2 times, mixing the filtrates after two times of decoction, and concentrating to final concentration of 2 g/mL. Making into powder by conventional method.
Example 3
18g of raw ephedra herb, 12g of cimicifuga foetida, 24g of angelica, 14g of rhizoma anemarrhenae, 15g of polygonatum, 15g of scutellaria baicalensis, 12g of radix paeoniae alba, 36g of radix asparagi, 26g of sweet wormwood, 30g of turtle shell, 15g of amomum tsao-ko, 18g of mangnolia officinalis, 8g of gypsum, 8g of rhizoma atractylodis and 8g of liquorice.
Pulverizing the above raw materials into fine powder, mixing, soaking for 30min, decocting for 2 times, mixing the filtrates after two times of decoction, and concentrating to final concentration of 2 g/mL. Making into ointment by conventional method.
Example 4
18g of raw ephedra herb, 18g of cimicifuga foetida, 20g of angelica, 8g of rhizoma anemarrhenae, 15g of polygonatum odoratum, 15g of scutellaria baicalensis, 12g of radix paeoniae alba, 12g of radix asparagi, 20g of sweet wormwood, 5g of turtle shell, 20g of amomum tsao-ko, 30g of magnolia officinalis, 35g of gypsum, 35g of rhizoma atractylodis and 15g of liquorice.
Pulverizing the above raw materials into fine powder, mixing, soaking for 30min, decocting for 2 times, mixing the two decoctions, filtering, and concentrating to final concentration of 2 g/mL. Making into aerosol by conventional method.
Example 5
8g of raw ephedra, 15g of cimicifuga foetida, 5g of angelica, 12g of rhizoma anemarrhenae, 25g of polygonatum, 25g of scutellaria, 20g of radix paeoniae alba, 20g of radix asparagi, 25g of sweet wormwood, 25g of turtle shell, 10g of amomum tsao-ko, 15g of mangnolia officinalis, 25g of gypsum, 15g of rhizoma atractylodis and 10g of liquorice.
Pulverizing the above raw materials into fine powder, mixing, soaking for 30min, decocting for 2 times, mixing the filtrates after two times of decoction, and concentrating to final concentration of 2 g/mL. Making into solution by conventional method.
Example 6
5g of raw ephedra herb, 5g of cimicifuga foetida, 5g of angelica, 5g of rhizoma anemarrhenae, 5g of polygonatum odoratum, 5g of scutellaria baicalensis, 5g of radix paeoniae alba, 5g of radix asparagi, 5g of sweet wormwood, 5g of turtle shell, 5g of amomum tsao-ko, 5g of magnolia officinalis, 5g of gypsum, 5g of rhizoma atractylodis and 5g of liquorice.
Pulverizing the above raw materials into fine powder, mixing, soaking for 30min, decocting for 2 times, mixing the two decoctions, filtering, and concentrating to final concentration of 2 g/mL. Making into pill by conventional method.
Example 7
6g of raw ephedra, 12g of cimicifuga foetida, 12g of angelica, 6g of rhizoma anemarrhenae, 6g of polygonatum, 24g of scutellaria, 24g of radix paeoniae alba, 36g of radix asparagi, 36g of sweet wormwood, 12g of turtle shell, 16g of amomum tsao-ko, 24g of mangnolia officinalis, 48g of gypsum, 6g of rhizoma atractylodis and 12g of liquorice.
Pulverizing the above raw materials into fine powder, mixing, soaking for 30min, decocting for 2 times, mixing the filtrates after two times of decoction, and concentrating to final concentration of 2 g/mL. Making into spray by conventional method.
Example 8
12g of raw ephedra herb, 12g of cimicifuga foetida, 22g of angelica, 16g of rhizoma anemarrhenae, 32g of polygonatum odoratum, 16g of scutellaria baicalensis, 16g of radix paeoniae alba, 16g of radix asparagi, 22g of sweet wormwood, 8g of turtle shell, 16g of amomum tsao-ko, 16g of magnolia officinalis, 32g of gypsum, 32g of rhizoma atractylodis and 12g of liquorice.
Pulverizing the above raw materials into fine powder, mixing, soaking for 30min, decocting for 2 times, mixing the filtrates after two times of decoction, and concentrating to final concentration of 2 g/mL. Making into injection by conventional method.
Example 9
10g of raw ephedra herb, 10g of cimicifuga foetida, 30g of angelica, 20g of rhizoma anemarrhenae, 40g of polygonatum odoratum, 30g of scutellaria baicalensis, 30g of radix paeoniae alba, 40g of radix asparagi, 40g of sweet wormwood, 40g of turtle shell, 20g of amomum tsao-ko, 30g of magnolia officinalis, 50g of gypsum, 40g of rhizoma atractylodis and 20g of liquorice.
Pulverizing the above raw materials into fine powder, mixing, soaking for 30min, decocting for 2 times, mixing the two decoctions, filtering, and concentrating to final concentration of 2 g/mL. Making into capsule by conventional method.
Example 10
20g of raw ephedra herb, 20g of cimicifuga foetida, 30g of angelica, 30g of rhizoma anemarrhenae, 40g of polygonatum odoratum, 30g of scutellaria baicalensis, 30g of radix paeoniae alba, 40g of radix asparagi, 40g of sweet wormwood, 40g of turtle shell, 20g of amomum tsao-ko, 30g of magnolia officinalis, 50g of gypsum, 40g of rhizoma atractylodis and 20g of liquorice.
Pulverizing the above raw materials into fine powder, mixing, soaking for 30min, decocting for 2 times, mixing the filtrates after two times of decoction, and concentrating to final concentration of 2 g/mL. Making into gel by conventional method.
Example 11
Influence of composition on pathological injury of rat tissue with acute lung injury induced by intestinal ischemia reperfusion
(1) Animals, drugs and instruments: 24 male Wistar rats purchased from beijing weitonglihua laboratory animal technology ltd, license number: SCXK (Jing) 2016 + 0006 and weighing 180-220 g. Approved by the ethical committee of experimental animals of Shanxi Chinese medicine university.
(2) An experimental instrument: non-invasive artery clamp (Beijing Yino Tai science and technology development Co., Ltd.), fecal DNA extraction kit (OMEGA-R6828, OMEGA Bio-Tek Co., USA), low speed centrifuge (Kogaku Innovation Co., Ltd., KDC-1044), ACQUITY UPLC BEH C18 chromatographic column (Tan. Tanskian chemical and physical research institute, AT. PEG-20M), high performance liquid chromatograph (Saimer Feishi science Co., Ltd., Ultimate3000), four-stage rod-electrostatic field trap high resolution mass spectrometer (Saimer Feishi science Co., Ltd., UHPLC-Q-active Orbitrap-MS).
(3) Establishing an animal model and administering: rats were randomized into 3 groups: sham (Sham), model (ALI), example 1 (example 1) group (28g kg)-1). Before molding, Sham and ALI were administered distilled water, and example 1 was drenched with the water decoction of example 1 for 3 days.
Injecting 10% chloral hydrate 0.2mL/100gb.w. into abdominal cavity, fixing in supine position, disinfecting with alcohol, taking a central incision of the abdominal cavity about 3cm, putting the intestinal canal into the abdominal cavity, pulling the intestinal canal to the outside of the body rightwards, wetting the exposed intestinal canal with gauze soaked by 0.9% normal saline, exposing and dissociating Superior Mesenteric Artery (SMA), returning the small intestine to the abdominal cavity after the small intestine is completely ischemic due to noninvasive artery clamping and closing SMA, and closing the abdominal operation incision. After the ischemia lasts for 1h, the noninvasive artery clamp is removed, the tissue recovers the blood supply for 2h, and the experiment is ended. The sham group did not clamp free SMA alone.
(4) Animal handling and sample taking: separating right lung, collecting right upper lung, carefully removing extrapulmonary tissue, rinsing with normal saline, sucking dry lung surface liquid with filter paper, immediately placing on an electronic balance, weighing, oven drying in a 60 deg.C oven for 48 hr to constant weight, and calculating (W/D) ratio. The lung tissue and the distal end of the colon are taken on ice, washed by ice physiological saline, fixed by 4% paraformaldehyde, embedded by paraffin and then sliced by HE for staining. The conditions of intrapulmonary hemorrhage, intra-alveolar inflammatory exudation and neutrophil infiltration, the thickening degree of alveolar walls, the formation of a hyaline membrane, etc. were observed and quantified by 0 to 4 integral (PI). And (3) collecting animal wastes, and analyzing the bacterial genome of the intestinal microorganisms of the sample by using a high-throughput sequencing method.
And (3) separating the right lung, taking the right upper lung, carefully removing extrapulmonary tissues, rinsing with normal saline, sucking dry lung surface liquid by using filter paper, immediately placing on an electronic balance, weighing, then placing in a 60 ℃ oven, drying for 48h to constant weight, and calculating the (W/D) ratio.
(5) Example 1 effect on the wet/dry weight ratio of lung tissue (shown in figure 1 as W/D change in intestinal ischemia reperfusion lung injury): the ALI group had increased W/D (P <0.01) compared to the Sham group, whereas example 1 had significantly decreased W/D after the dry prognosis (P <0.01), suggesting that example 1 may be effective in reducing lung injury caused by ischemia-reperfusion of the intestine.
(6) Example 1 effect on lung pathology (as shown in fig. 2 pathomorphology of intestinal ischemia-reperfusion lung injury): HE staining is carried out on the lung and colon far-end tissues of rats, and extensive lung tissue necrosis can be seen in the ALI group; in example 1, the arteriolar lumen was dilated, thrombus was formed, and no abnormality was found in the alveoli and bronchioles.
Pathological results of distal colon tissues show that the ALI group has extensive necrosis of intestinal mucosa and submucosa, muscle layer infiltration of inflammatory cells and fat necrosis; no change was observed in the mucosa of the group of example 1, and vasodilation, congestion, edema due to interstitial porosity, normal muscle layer and serosal structure were observed under the mucosa.
(7) Example 1 Effect on the expression levels of TLR4, My D88, TRAF6 proteins (as shown in FIG. 3, FIG. 3 shows the expression profiles of TLR4, My D88, TRAF6 proteins (group A: Sham; group B: ALI; group C: QYF)): compared with Sham group, the expression levels of TLR4, MyD88, TRAF6 were significantly increased in the lung tissue of rats in ALI group, while TLR4, My D88, TRAF6 expression appeared to be decreased to a different extent in rat lung tissue after treatment of example 1 (P < 0.05).
Second, example 1 mechanism of action for suppressing acute lung injury due to intestinal ischemia-reperfusion through intestinal flora modulation
Two-way conversation driven by the metabolic state of the microbiota is critical to maintaining the health and homeostasis of individual hosts, and the dysregulation of these dynamics is a key driver of many diseases, and therefore research directed at metabolic pathways of the microflora may provide new strategies for treating ALI. Studies have shown that disturbances in the intestinal flora affect lung disease through the gut-lung axis. Gut dysbiosis may increase the risk of translocation of the flora by disrupting the integrity of the gut barrier. If the flora leaving the intestinal tract migrates to the lungs, the immune system in the lungs is activated, thereby exacerbating the immune damage to the lungs.
(1) Animal experiment and sequencing analysis of acute lung injury caused by intestinal ischemia reperfusion: constructing an acute lung injury model, grouping, feeding medicine, killing, and taking serum and colon tissues as before. Reference NEB
Figure BDA0003558859470000081
UltraTMDNA Library Prep Kit for
Figure BDA0003558859470000082
Extracting rat feces and genome DNA, carrying out PCR amplification and purification, and establishing a library of qualified samples. Sequencing the intestinal microbial genome of the sample by using an Illumina HiSeq high-throughput sequencing platform.
(2) Example 1 effect on species classification and composition of gut microbiota: comparing the clear Reads of each sample with the non-redundant gene set by using Bowtie2, and obtaining the abundance of each gene in the sample by using Samtools, we can obtain the relative abundance (relative abundance) of the flora at the level of Kingdom, Phylum (Phyum), Class (Class), Order (Order), Family (Family), Genus (Genus) and Species (specials); and performing Alpha diversity calculation, Beta diversity analysis, comparison of the difference of relative abundance of the floras among groups, heat map analysis and differential species screening on the species in the sample.
The gene protein sequences were aligned to the NCBI-Nr database using the DIAMOND software to obtain species classification annotation information. The sequencing sequences of the samples were compared at the species level and found to be absolutely superior at the phylum level (as shown in the species classification chart of the Illumina sequencing result of FIG. 4 (K: kingdom; P: phylum; C: class; O: order; F: family; G: genus; S: species)); order level, Clostridiales (Clostridiales), Lactobacillales (Lactobacillales) under Firmicutes; at the family level, Bacteroidaceae (Bacteroidaceae) and Prevoteriaceae (Prevotellaceae) are more abundant.
The composition of rat intestinal microorganisms at phylum and genus levels after acute lung injury caused by intestinal ischemia-reperfusion is obviously different from that of a sham operation group (as shown in fig. 5 and 6, fig. 5 is a graph of intestinal flora composition change (phylum level relative abundance) of rats with intestinal ischemia-reperfusion lung injury, and fig. 6 is a graph of intestinal flora composition change (genus level relative abundance) of rats with intestinal ischemia-reperfusion lung injury). Intestinal ischemia-reperfusion results in changes in intestinal microbial composition, overall reduction in species diversity, and positive correlation between the degree of intestinal dysfunction and the degree of lung injury, and is critical to microbiota changes. After the intervention of example 1, the intestinal firmicutes of the rats are increased, the bacteroidetes is reduced, and the ratio of the firmicutes to the bacteroidetes is increased; the relative reduction of Prevotella, the relative abundance of Lactobacillus and Bifidobacterium and the increase of Clostridium, and the diversity of ALI rat intestinal microorganisms can be restored to a certain extent by example 1.
Firmicutes can produce SCFAs which are directly utilized and absorbed by the body, and are the main butyrate producing flora. Lactobacillus acts as a probiotic and prevents airway inflammation caused by respiratory syncytial virus infection, and Clostridium enhances resistance to lung infection by Nod2 and GM-CSF. Prevotella species have recognized pathogenicity for pulmonary infection to promote viral infection, inducing IL-6 production. Clostridia are butyrate-producing intestinal probiotics that inhibit the growth of harmful gastrointestinal bacteria. According to the experiment, the Thenobacteriophytes and Bacteroides in the acute lung injury group are reduced, the Bacteroides, Prevotella and Lactobacillus are relatively reduced, the Shannon index is reduced, and the Simpson index is increased, so that the diversity of the relative floras in the acute lung injury group after the intestinal ischemia-reperfusion treatment is reduced. While the diversity of intestinal flora can be recovered to a certain degree in the embodiment 1, the embodiment 1 can prevent the colonization of pathogenic bacteria by adjusting the structural distribution and the composition of the intestinal flora and by up-regulating the immune response of organisms. The colony structure composition was further found to be similar in the Sham group and example 1 group samples in the clustering tree and PCoA analyses. Example 1 can improve the imbalance of intestinal flora to a certain extent, increase beneficial flora capable of producing short-chain fatty acids, inhibit harmful flora, and play a positive role in adjusting flora.
Species heatmap analysis was performed based on species composition and relative abundance of each sample (as shown in figure 7). And (4) selecting the genus with the top abundance of 20, and performing clustering analysis by using R language. As can be seen from the figure, the samples of example 1 after drug treatment are closer to each other, have higher similarity of microbial composition and abundance, and are separated from the samples of the model group.
(3) And comparing by using databases such as KEGG, GO, COG and the like to obtain species annotation information and function annotation information of the gene, and obtaining functions and species abundance. From the results of the functional annotation of KEGG, the intestinal flora function of rats with acute lung injury is closely related to the dysregulation of basic metabolic pathways such as Carbohydrate metabolism, Amino acid metabolism, Energy metabolism, nuclear metabolism, and metabolic process. Intestinal microbiota has metabolic activity in addition to nutrition from dietary carbohydrates, such as streptococcus pentosus can increase the antioxidant activity of fermented milk, and by producing SCFAs, anaerobic microorganisms in the colon, such as bacteroides, rotkia, bifidobacteria, etc., ferment indigestible carbohydrates, positively affecting differentiation and proliferation of intestinal epithelial cells. COG databases indicate that changes in gut microbiota may ameliorate the 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 of the acute lung injury rats treated in example 1 was closely related to these metabolic pathways.
Gut microbes can also affect the host immune system through cytokine signaling. The symbiotic microbiota stimulates TLR4 signaling, activating the transcription factor nuclear factor kappa light chain enhancer of activated B cells (NF- κ B) by myeloid differentiation primary response protein (MyD88) to induce pro-inflammatory gene expression. While the host's innate immune system (i.e., TLR4, 2, 5 receptors, and NLRP3) affects the composition of microbiota, gut inflammation and immune activation secondary to gut dysbiosis or gut barrier dysfunction may also further lead to gut, systemic immune inflammatory responses through a variety of underlying mechanisms. Microbial-derived stimuli are key mediators of inflammatory responses, and participate in gut-lung signaling. Intestinal microbiota restricts translocation of the microbiota from the intestinal lumen to the circulatory system by its structural components and metabolites, preventing systemic immune response. Gut microbiota acts as a trigger for TLR4 signaling, inducing TLR signaling during small bowel ischemia, further activating a complex signaling cascade, recruiting the adaptor molecule MyD88), causing acute bowel, lung injury, inflammation, and endothelial injury. TRAF6 is a downstream signal of the TLR/IL-1R superfamily, further regulating immune responses.
(4) Example 1 effect on metabolism (shown in FIG. 8 relative content of differential metabolites in rat serum): rat serum samples were subjected to metabolic profiling using a UHPLC-Q-active Orbitrap-MS based method, followed by multivariate analysis to determine key biomarkers, and 19 potential characteristic metabolites after ALI group and example 1 treatment were obtained. Metabolites such as the choline metabolites Trimethylamine (TMA), secondary BA, deoxycholic acid (DCA), and SCFA in the host cannot be produced without bacterial fermentation. Ether lipids are capable of regulating cell differentiation, affecting cell signaling, and acting as potential endogenous antioxidants by reducing oxidative stress, and plasmalogens have a protective effect on oxidative damage. Pan released by intestinal microbiome is a limiting precursor of CoA synthesis in cells, and Pan and cysteamine have good regulation and control effects on sustained metabolism, oxidation or hypoxia stress of tissues in many chronic inflammatory diseases, so that cell damage induced by ROS is limited. Example 1 anti-inflammatory and immunomodulatory effects may be achieved by down-regulating Platelet-activating factor, up-regulating d-pantonic acid, affecting ether lipid metabolism and the pantothenic acid and coenzyme A metabolic pathways.
Example 12
The experiment of example 11 was conducted in place of example 1 in examples 2 to 10, and similarly, the effects of effectively reducing lung injury caused by ischemia-reperfusion of the intestine, suppressing luminal dilatation and thrombosis of pulmonary arterioles, protecting the tissue structure of alveoli and bronchioles, and maintaining the normal structure of the intestinal mucosal muscularis and serosa were 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. Improve the imbalance of intestinal flora, increase beneficial flora capable of producing short-chain fatty acid, inhibit harmful flora, and regulate flora. Has obvious treatment effect on acute lung injury and good clinical application prospect.
Those skilled in the art will appreciate that the invention may be practiced without these specific details. Although illustrative embodiments of the present invention have been described above to facilitate the 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, and various changes may be made apparent to those skilled in the art as long as they are within the spirit and scope of the present invention as defined and defined by the appended claims, and all matters of the invention which utilize the inventive concepts are protected.

Claims (7)

1. A traditional Chinese medicine composition for treating acute lung injury is characterized in that: the traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 5-20 parts of raw ephedra herb, 5-20 parts of cimicifuga foetida, 5-30 parts of angelica sinensis, 5-30 parts of rhizoma anemarrhenae, 5-40 parts of polygonatum odoratum, 5-30 parts of scutellaria baicalensis, 5-30 parts of radix paeoniae alba, 5-40 parts of asparagus, 5-40 parts of sweet wormwood, 5-40 parts of turtle shell, 5-20 parts of amomum tsao-ko, 5-30 parts of mangnolia officinalis, 5-50 parts of gypsum, 5-40 parts of rhizoma atractylodis and 5-20 parts of liquorice.
2. The traditional Chinese medicine composition for treating acute lung injury according to claim 1, wherein: the traditional Chinese medicine composition is prepared from the following raw material medicines 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 polygonatum, 5-30 parts of scutellaria baicalensis, 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 amomum tsao-ko, 5-30 parts of mangnolia 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, which is characterized in that: the traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 10 parts of raw ephedra, 10 parts of rhizoma cimicifugae, 15 parts of angelica sinensis, 15 parts of rhizoma anemarrhenae, 30 parts of radix polygonati officinalis, 15 parts of scutellaria baicalensis, 15 parts of radix paeoniae alba, 30 parts of radix asparagi, 30 parts of sweet wormwood, 30 parts of turtle shell, 10 parts of amomum tsao-ko, 15 parts of mangnolia officinalis, 30 parts of gypsum, 30 parts of rhizoma atractylodis and 10 parts of liquorice.
4. The preparation method of the traditional Chinese medicine composition for treating acute lung injury according to any one of claims 1 to 3, which is characterized by comprising 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 filtrates after decocting for two times, and concentrating to final concentration of 2 g/mL.
5. Use of a Chinese medicinal composition according to any one of claims 1 to 3 in the preparation of a medicament for the treatment of acute lung injury.
6. The use of the Chinese medicinal composition of claim 5 in the preparation of a medicament for the treatment of acute lung injury: the method is characterized in that: the traditional Chinese medicine composition comprises a liquid preparation, a solid preparation, a semisolid preparation and a gas preparation.
7. The use of the Chinese medicinal composition according to claim 6 in the preparation of a medicament for the treatment of acute lung injury: the method is characterized in that: the liquid dosage form comprises: aromatic water, solution, injection, mixture, lotion, and liniment; the solid dosage forms comprise powder, pill, tablet, pellicle, capsule, and granule; the semi-solid dosage form comprises: ointments, pastes, gels; the gaseous dosage form comprises: aerosol and spray.
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