The Mechanism Of Shenqi Yangxin Decoction In The Treatment Of Dilated Cardiomyopathy Based On Intestinal Flora

OBJECTIVE:To investigate whether there is a difference between the intestinal flora of DCM model rats and normal rats through animal experiments;to explore whether Shenqi Yangxin Decoction can change the abundance and structural distribution of the intestinal flora of rats with dilated cardiomyopathy,And then affect the expression of TLR-4/NF-κB mRNA in the myocardial tissue of DCM model rats,achieve the therapeutic goals of improving cardiac function and myocardial injury in DCM model rats,and provide a new entry point and research direction for the treatment of DCM.Methods:Forty-five male rats were injected intraperitoneally with adriamycin to construct a DCM model.After 8 weeks,the success of the model was evaluated.The successfully modeled rats were randomly divided into model group,metoprolol group,Shenyangxin decoction group,The perindopril group and the normal group were set up separately.Each group in the treatment group was given corresponding drugs according to body weight every day.Metoprolol tablets 50mg/kg(twice a day),Shenqi Yangxin decoction 1.87g/kg·d,Indopril tablets 3mg/kg·d for 8 weeks.During the intervention period,the model group and the normal group were given an equal volume of normal saline intragastrically.After the experiment,the rats in each group were anesthetized to collect cardiac color Doppler ultrasound data,including left ventricular end diastolic diameter(LVEDD),left ventricular systolic diameter(LVESD),short axis contraction rate(FS),left ventricular ejection fraction(LVEF)After fasting for 24 hours,anesthesia,blood sampling and death,ELISA to determine serum brain natriuretic peptide(BNP),troponin I(cTnI);save heart tissue,cryopreservation,use RT-PCR method to determine TOLL samples in myocardial tissue Receptor 4(TLR-4)and nuclear factor kappa B(NF-κB)mRNA expression levels;the colonic feces of the dilated cardiomyopathy model group,the Shenqi Yangxin decoction intervention group and the normal group were collected for 16S amplification and sequencing,Observe the difference of intestinal flora between the three groups.Results:1.Compared with the normal group,the value of color Doppler ultrasound LVEDD and LVESD in the model group increased,and the LVEF and FS decreased(P<0.05 for each group data),the difference was statistically significant;compared with the model group,perindopril The LVEDD and LVESD values of cardiac color Doppler ultrasound in the Li group,Metoprolol group,and Shenqi Yangxin decoction group decreased,while LVEF and FS increased(comparison between the data of each drug intervention group and the model group,P<0.05),and the difference was statistically significant.2.Compared with the normal group,the rat heart color Doppler ultrasound serum BNP and cTnI levels in the model group increased(P<0.05 for each group),and the difference was statistically significant;compared with the model group,the perindopril group and metoprolol The scrum BNP and cTnI levels of the Shenqi Yangxin Decoction group and the Shenqi Yangxin Decoction group decreased(the data of each drug intervention group was compared with the model group,P<0.05),and the difference was statistically significant.3.Compared with the normal group,the expression levels of TLR-4 and NF-κB mRNA in the myocardial tissue of the model group were increased(P<0.05 for each group),and the difference was statistically significant;compared with the model group,the perindopril group,The expression levels of TLR-4 and NF-κB mRNA in myocardial tissue of the Metoprolol group and the Shenqi Yangxin Decoction group decreased(the data of each drug intervention group were compared with the model group,P<0.05),and the difference was statistically significant.4.Compared with the normal group,the diversity of the intestinal flora of the model group increased,P<0.05,the difference was statistically significant,and the uniformity of the flora increased,but P>0.05,the difference was not statistically significant;the intestinal bacteria of the model group At the phylum level,Firmicutes and Moraxellaceae decreased significantly,and Verrucomicrobia and Proteobacteria were significantly enriched;at the genus level,the intestinal tract of the model group The flora of Lactobacillus,Ruminiclostridium 6,Anaerofilum,Roseburia,Psychrobacter,Odribacter,Eubacterium xylanophilum group decreased significantly,while the model group was enriched in Romboustia,Eubacterium coprostanoligenes,Clostridium sensu stricto 1,Pasteurella,Bifidobacterium,Doumrea,Flercaliutculia,Adlercrebaculia,etc.5.Compared with the model group,in the Shenqi Yangxin Decoction group,the diversity and uniformity of the flora increased,P<0.05,the difference was statistically significant;at the phylum level,the Actinobacteria(Actinobacteria)decreased significantly,while Bacteroidates showed enrichment;at the genus level,the Shenqi Yangxin Decoction group had a significant decrease in Romboustia,Eubacterium coprostanoligenes,Clostridium sensu stricto 1,Pasteurella,Bifidobacterium,Dorea,Adlercreutzia,Faecalibaculum and other genera.9.Oscillibacter,Ruminiclostridium,Anaerovorax,Tyzzerella,Ruminclostridium,Intestinimonas and other genera are significantly enriched.6.Blautia,Lactococcus,Romboutsia,Ruminococcaceae UCG-013,[Eubacterium]Coprostanoligenes group,Lachnospiraceae UCG-006,Pasteurella are positively correlated with the expression level of TLR-4 mRNA at the genus level;are positively correlated with the expression level of NF-κB mRNA There are Akkermansia,Lachnospiraceae UCG-006,Pasteurella,Turicibacter,[Eubacterium]Coprostanoligenes group,Romboutsia,Ruminococcaceae UC G-013,Clostridium sensu stricto 1;In addition,Ruminiclostrrdium 6 is negatively correlated with TLR-4 mRNA and NF-κB mRNA expression levels.Conclusion:1.Shenqi Yangxin Decoction can reduce the left ventricular end-diastolic diameter and left ventricular systolic diameter in DCM rats,improve left ventricular ejection fraction and short axis shortening rate,and reduce serum brain natriuretic peptide and troponin I levels.Improve myocardial activity and effectively treat dilated cardiomyopathy.2.Shenqi Yangxin Decoction can down-regulate the levels of TLR-4 and NF-κB mRNA in myocardium and reduce myocardial inflammation.3.There are differences in the abundance and distribution structure of intestinal flora between DCM model rats and normal rats.4.Shenqi Yangxin Decoction can change the abundance and structural distribution of the intestinal flora of DCM rats,and these changes may directly or indirectly reduce the expression of TLR-4 and NF-κB mRNA in the myocardium,thereby improving myocardial inflammation Response,myocardial remodeling,improve cardiac contractility,and achieve therapeutic goals.