| Objective:In order to provide a theoretical basis for follow-up clinic and experiment,this study systematically combed the studies of heart failure based on the theoretical guidance of "the relationship between heart and spleen" at the first,then summarized Professor Cui Xiangning’s knowledges.In addition,the correlation between heart failure and inflammatory response and gut microbiota in modern research were also be combined.Secondly,the efficacy and safety of Jianpi Yixin Formula were objectively evaluated through the observation in HF patients who were treated.Finally,the study explored and analyzed the effect of Jianpi Yixin Formula on gut microbiota and inflammatory response in heart failure rat model,and clarified the potential mechanism of Jianpi Yixin Formula.Methods:1.Clinical efficacy evaluation: 70 patients who diagnosed with chronic heart failure with deficiency of heart and spleen and combination of water and blood stasis were randomly divided into experimental group and control group.The control group was treated with conventional western medicine,while the experimental group was treated with Jianpi Yixin Formula for 8 weeks.The NYHA grade,Lee’s score of heart failure,TCM syndrome score,NT-pro BNP,6MWT,hs-CRP,echocardiography,MLHFQ,hepatic and renal function,blood and urine and bowel routine were observed and recorded before and after treatment.Finally,the statistical analysis was carried out.2.Animals experimental study: Through ligating of anterior descending coronary artery,50 SD rats were selected for inducing and establishing the model of heart failure.The rats were divided into sham group,model group,Jianpi Yixin Formula group and DMB group and then intervened for 4 weeks.The echocardiography of rat were measured before sampling,and then the myocardial pathology,myocardial fibrosis,inflammatory factors levels,gut microbiota and the metabolites were detected by HE and Masson staining,Western Blot,immunohistochemistry,16 S r DNA sequencing and LC-MS.Results:1.Clinical efficacy evaluation: In the evaluation of cardiac function,the total effective rate of the experimental group and the control group was 84.85% and 78.79% respectively,and the former was higher.And Lee’s heart failure score,TCM syndrome score,NT-pro BNP,hs-CRP,6WMT and MLHFQ were significantly improved after treatment.It was found that the effect of the experimental group was better in comparison(P<0.05).There were significant differences in the data of before and after treatment(P<0.01),while not statistically significant between the comparison of two groups(P>0.05)in LVEF and LVD.In addition,the results also shown that there were no adverse reactions in whole experiment.2.Animals experimental study: Firstly,Jianpi Yixin Formula could significantly improve the cardiac function including increasing LVEF,FS and reducing LVIDs(P<0.05),but there is no statistical significance in reducing LVIDd in HF rats.At the same time,it could also improve cardiomyocyte morphology,decrease HW/BW and delay myocardial fibrosis.Secondly,in HF rats,16 sr DNA sequencing showed that the intervention of Jianpi Yixin Formula at some extent could enrich the diversity of gut microbiota and regulate the relative abundance at different classification levels such as phylum,class,order,family,genus and species,especially the significant increase of ACE,Chao1,Shannon and Simpson index(P<0.05);LEfse analysis showed that the biomarkers representing the gut structure characteristics of Jianpi Yixin Formula were Oscillospirales,Eubacterium coprostanoligenes group and NK4A214 group,and it was found that the functional genes of Jianpi Yixin Formula had more obvious advantages in Organismal Systems,Metabolism,Cellular Processes.Additionally,Jianpi Yixin Formula also decreased the level of TMAO,repaired the damaged colon tissues and increased the protein expression level of tight junction protein such as occludin,which suggested that Jianpi Yixin Formula protect the intestinal barrier to a certain extent.Thirdly,Western blot showed that Jianpi Yixin Formula could decrease the expression of inflammatory factors including NLRP3,ASC,c-IL-1β,IL-1β,NF-κB,TNF-α and IL-6(P<0.05).Except for TNF-α,the others were statistically significant.This result suggested that the inflammatory response was alleviated after the intervention of Jianpi Yixin Formula in HF rats.Moreover,the formula also played an important role in inhibiting the activation of TGF-β1/Smad3 pathway and attenuating myocardial fibrosis.Conclusion:1.Theoretical studies showed that the treatment of heart failure based on "heart and spleen correlation" is justified,and Jianpi Yi Xin Formula has an adequate cubic basis.Meanwhile,a significant correlation has been confirmed between heart failure and inflammatory response and gut microbiota in modern researches,which has laid a theoretical foundation for subsequent intervention of heart failure by inhibiting inflammatory response and regulating gut microbiota.2.Clinical efficacy evaluation showed that the clinical symptoms,activity tolerance and quality of life were significantly improved in HF patients after treatment.It means that Jianpi Yixin Formula has obvious advantages in improving cardiac function and reducing inflammation response.So far,its adverse reactions and side effects have not been found.Given its advantages,it is worthy of further research and application.3.Animal experiments showed that the mechanism of Jianpi Yixin Formula involves in regulating gut microbiota and metabolites,protecting intestinal barrier and inhibiting NLRP3-mediated inflammation,which in order to improve cardiac function and delay the process of myocardial fibrosis in HF rats. |
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