| Chronic heart failure(CHF) is the end-stage of all sort of heart disease.As the population is aging,morbidity rate of CHF is getting higher and higher,which becomes a international problem of public health.The guidelines for CHF improve the level of treating CHF,but the mortality and morbidity is still high.The unsatisfactory therapy effect makes people search for better method for treating CHF, the energy metabolism of cardiomyocyte is one of the hot spots,though there is not any generally acknowledged medicine which is against this target.The principle of Traditional Chinese medicine,which treat CHF by replenishing Qi,has something in common with improving the of energy metabolism of failed heart.In resent decades,a lot of clinical and experimental trials have been carried out, which showed us the satisfactory results.But these results have not been systematically evaluated,the generalization and utilization of which is limited up to a certain extent.Radix astragali injection is the extractive of Radix astragali which is the deputy medicine of Qi-tonics.This injection is being generally used for treating CHF.In this thesis,a systematic review of clinical studies on treating CHF with Radix astragali injection will be performed,and some cellular and molecular biological experiments will be executed to investigate the relationship of mechanism of treating with Radix astragali injection and energy transportation of cardiomyocyte.We are aimed to find some evidence-base clinical and experimental evidence for treating CHF by replenishing Qi,and do some significant exploration in searching for the medicine which is able to improving energy metabolism of cardiomyocyte.1 Radix astragali injection for CHF:a systematic review and meta analysisMethods:(1)Search items were:(Title:Radix astragali injection) AND(Title: cardiac insufficiency or heart failure or cardiac failure),the search was applied to the CBM database(the publication date was not limited);(2)Literature bolting was performed by 2 reviewers independently,different opinions would be solved through negotiation;(3)The relation data of literatures were extracted and evaluated;(4)A meta analysis was performed based on qualified randomized blind controlled trials(RCTs).Results:(1) 246 literatures were found out;(2) Through twice bolting,there were 117 literatures met the evaluate procedure.(3) There were many defects in the enrolled literatures.There were 8 literatures' Jadad scores were 1,2 literatures' Jadad scores were 2,and there were not any literature's Jadad score was higher than 2. These 10 literatures contained 10 RCTs which were enrolled into Meta analysis (711.cases).(4) The result of analysis showed that compared with routine therapy, additional of use of Radix astragali injection could raise left ventricular ejection fraction(LVEF)(P＜0.001),cardiac output(CO)(P＜0.00001),cardiac index(CI)(P＜0.00001) and effective rate(P＜0.001) significantly,but not significantly compared with additional of use of nitroglycerine;Two RCTs which used Simpson method enrolled into Meta analysis,and the result showed that compared with routine therapy, additional use of Radix astragali injection couldn't raised LVEF significantly(P=0.67); Compared with additional use of nitroglycerine,additional use of Radix astragali injection couldn't lower the mortality and incidence of arrhythmia(P＞0.05);There was no significant difference between routine therapy and additional use of Radix astragali injection in left ventricular end diastolic or systolic volume and E/A(P=0.17, 0.21,0.75).Conclusion:Additional use of Radix astragali injection could improve the function of heart more effectively.However,According to this Meta analysis,we can't get final answer.We need high qualitative multicenter clinical trial of which the sample is large to evaluate the therapy effective for treating CHF with Radix astragali injection.The clinical trials which treat CHF with Radix astragali injection should improve their technology quality.The following aspects should be improved,such as strict criterion for enrolling,treatment based on syndrome differentiation,searching for suitable positive control or placebo and the way for executing blind method, choosing proper index for evaluating therapy effective,establishing consummate system for evaluating therapy effective,complete follow-up and side-effect reports.2 The effect of Radix astragali injection on energy metabolism of hypertrophic cardiomyocyteMethods:To establish the model of hypertrophic cardiomyocyte,we stimulated the cardiomyocytes of neonatal rat which were primarily cultured in vitro with angiotensin(AngⅡ).The cardiomyocytes were divided into 4 groups:control group, model group,Losartan group and Radix astragali injection group.At 24h and 48h,We investigated the effects of AngⅡ,Losartan and Radix astragali injection,on mitochondrial membrane potential(MMP) of cardiomyocytes by confocal microscopy, on the activity of total creatine kinase(CK) by means of biochemistry method and on CK isoenzymes which were separated using Rapid Electrophoresis system,and on B-CK,M-CK,mi-CK,iso-adenine nucleotide translocator(ANT) mRNA gene expression by using RT-PCR.Results:(1) At 24h,MMP of model group was obviously reduced compared with control(P＜0.01),Radix astragali injection and Losartan could raise MMP,MMP of the cardiomyocytes stimulated by Radix astragali injection was higher than control group significantly(P＜0.01);at 48h,MMP of model group was continually reduced significantly(P＜0.01),the difference among other groups was not significantly.(2) ANT 1 mRNA gene expression of hypertrophic cardiomyocytes were lower,at 48h the difference between model group and control Was significant(P＜0.01),and Radix astragali injection could remain it at the normal level.ANT 2 mRNA gene expressions of hypertrophic cardiomyocytes remained the same with the control.At 24h,Radix astragali injection could raise the level of ANT 2 mRNA gene expression significantly(P＜0.01) and at the 48h not significantly.(3) At 24h,the levels of CK-M mRNA gene expressions(P＜0.05) and the content of CK-MM(P＜0.01) of hypertrophic cardiomyocytes were reduced obviously,at the same time the levels of CK-B mRNA gene expressions and the content of CK-BB were raised significantly(P＜0.01).There were no difference in the content of CK-MB and total CK activity among these groups.At 48h,the level of CK-M mRNA gene expressions of model group was continually reduced,while the levels of the groups treated with Radix astragali injection and Losartan were normalized.The content of CK-MM of model group and L group were raised significantly(P＜0.01),while the content of the group treated with Radix astragali injection remained normal.The level of CK-B mRNA gene expressions and the content of CK-BB of model group were still high(P＜0.01), and there was no difference in the content of CK-BB among other groups.The content of CK-MB of L group was higher than control group obviously(P＜0.05).Total CK activity of model group was depressed significantly(P＜0.01),and Radix astragali injection and Losartan could prevent it from being reduced.Conclusion:The MMP of hypertrophic cardiomyocytes were obviously reduced compared with control,while the activated fetal program made the content of CK change.The level of ANT 1 mRNA gene expressions and CK activity of failed cardiomyocytes decreased.These changes showed that dysfunction of energy metabolism especially energy transportation emerged.Losartan and Radix astragali injection could improved this dysfunction.According to research above,we infer that the mechanism of improving heart function with Radix astragali injection may be concern with stabilizing the enzymes used for transporting energy substances and MMP so as to improving diastolic and systolic function.
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