Meta Analysis And Mechanism Study Of Sini Decoction In The Treatment Of Chronic Heart Failure

ObjectiveClinical study: To systematically review the efficacy of sini decoction for chronic heart failure.Experimental study: To observe the efficacy of the Chinese herbal formula SiniTang(SNT)in heart failure after myocardial infarction in rats and investigate the specific mechanism.MethodsClinical study: RCTs about comparision between sini decoction with routine treatment of western medicine and simple routine treatment of western medicine for chronic heart failure.Were collected from PubMed,The Cochrane Library,EMbase,Web of Science,Chinese Biomedical Literature Database,WanFang Data,VIP and CNKI.MeSH subject words and free words were used in the retrieval method,and the English retrieval words included "sini decoction","chronic heart failure","randomized controlled trial".The Chinese retrieval words included "four inverse decoction","chronic heart failure","randomized controlled trial".The endpoints of this meta analysis included clinical efficacy,left ventricular ejection fraction(LVEF),the level of BNP,the level of NT-ProBNP,6-minute walking test,mortality,adverse reaction rate and TCM syndrome score.Cochrane criteria was used for literature quality evaluation,including randomization protocol,grouping concealment,blind method,data integrity,selective reporting and other bias.When the heterogeneity was less than 50%,the fixed effect model was used.When the heterogeneity was more than 50%,the random effect model was used.Sensitivity analysis and subgroup analysis were performed according to the clinical follow-up time.Begg test and funnel plot were used to assess the publication bia.Experimental study: We established the animal model of heart failure after myocardial infarction in SD rats by ligating the anterior descending branch of left coronary artery.After 4weeks,rats with left ventricular ejection fraction <50% were screened by echocardiography.Rats were randomly divided into six experimental groups: Sham operation group,HF group,Benazepril group,high dose of SNT group,medium dose of SNT group and low dose of SNT group.Drugs were administered by oral gavage for eight weeks and the heart funtion was detected by echocardiogram.Ria method was used to detect the level of plasma renin,angiotensin ? and aldosterone.The expression levels of angiotensin converting enzyme and angiotensin receptor II were detected by Western blot and qRT-PCR in order to explore the specific mechanism.ResultsClinical study: 30 RCTs were included in this Meta analysis.The sini decoction with routine treatment of western medicine group included 1143 patients and the simple routine treatment of western medicine group included 1101 patients.The result of meta-analysis showed that the sini decoction with routine treatment of western medicine significantly improved the clinical efficacy(P<0.05);LVEF was significantly increased(P<0.05);the level of BNP was significantly decreased(P<0.05);the level of NT-ProBNP was significantly decreased(P<0.05);the 6-minute walking test was significantly extended(P<0.05);the mortality was significantly reduced(P<0.05);the TCM syndrome score was significantly decreased(P<0.05);the adverse reactions were reduced without statistically significant difference(P>0.05).The subgroup analysis was conducted according to the clinical follow-up time.The results showed that during less than 1 month of follow-up,the clinical efficacy of the sini decoction with routine treatment of western medicine group was significantly higher than that of the simple routine treatment of western medicine group(P<0.05);the LVEF was significantly higher(P<0.05).During 2-6 months of follow-up,the clinical efficacy of the sini decoction with routine treatment of western medicine group was significantly higher than that of the simple routine treatment of western medicine group(P<0.05);the LVEF was significantly higher(P<0.05).During 7-12 months of follow-up,the clinical efficacy of the sini decoction with routine treatment of western medicine group was significantly higher than that of the simple routine treatment of western medicine group(P<0.05),but the LVEF was higher than that of the control group without statistically significant difference(P>0.05).Experimental study: The outcomes of this study indicated that SNT significantly decreased the heart rate(P<0.05),improved the LVEF and LVFS(P<0.05),but the E/A and E'/A' had no significant difference when compared with control group.SNT significantly thickened both LVAWd and LVAWs(P<0.05),and reduced LVIDs(P<0.05)when compared with control group.SNT significantly reduced the left ventricular quality index(P<0.05),Collagen Volume Fraction(P<0.05)and decreased the level of Plasma Renin,Angiotensin II,and Aldosterone(P<0.05).SNT significantly down regulated the protein and gene level of ACE and AT1R(P<0.05).ConclusionClinical study: Based on the results of this meta-analysis,sini decoction with routine treatment of western medicine can significantly improve the clinical efficacy of patients with chronic heart failure,increased LVEF and 6 minutes walk test,reduce the level of BNP,NT-ProBNP,mortality,and TCM syndrome score.Therefore,sini decoction with routine treatmentof western medicine was better than simple routine treatment of western medicine for chronic heart failure.Experimental study: Sini decoction can significantly improve the heart function of rats with chronic heart failure after myocardial infarction,and its specific mechanism is closely related to the inhibition of renin-angiotensin-aldosterone system.