| Purpose:1 Use Meta analysis to evaluate the clinical efficacy of the method of invigorating the kidney and activating blood in the treatment of chronic heart failure,and provide evidence-based medicine for clinical practice.2 Based on the theory of "intercourse between heart and kidney"as a guide,a compound prescription for invigorating the kidney and activating blood was established,and the left anterior descending coronary artery ligation combined with reducing the food intake and exhaustive swimming were used to establish a rat model of chronic heart failure after myocardial infarction.The effects of cardiac function and the expression of myocardial fibrosis indexes of type ? collagen(Col I),type ? collagen(Col?)and ?-smooth muscle actin(?-SMA)in rats with chronic heart failure.3 This study intends to take the myocardial fibrosis mediated by the Wnt/?-catenin pathway as the entry point,aiming to reveal the potential effect mechanism of Bushen Huoxue compound on myocardial fibrosis in rats with chronic heart failure after myocardial infarction.Materials and methods:1 Meta-analysis of the clinical efficacy of the method of invigorating the kidney and promoting blood circulation combined with western medicine in the treatment of chronic heart failureComputer search of China Knowledge Network Database(CNKI),VIP Chinese Science and Technology Journal Full-text Database(VIP),Wan Fang Data,Chinese Biomedical Document Service System(SinoMed),PubMed,Cochrane Library,Web of Science,Embase,Clinical Trials-gov.The search time limit was from the establishment of the database to February 1,2021,randomized controlled clinical trials of the treatment of chronic heart failure by the method of tonifying the kidney and activating blood were included.The control group was treated with conventional western medicine,and the experimental group was treated with the method of tonifying the kidney and activating blood on the basis of the control group.The quality evaluation and data extraction of methods recommended in the included literature reference Cochrane Handbook 5.3,etc.,were used for Meta analysis with Revman 5.3 software,and the results were presented as forest maps,and funnel maps were used to assess whether there was publication bias.2 Effect of Bushen Huoxue Compound on cardiac function and expression of myocardial fibrosis in rats with chronic heart failure after myocardial infarction2.1 Establish a rat model of chronic heart failure after myocardial infarction and evaluate whether the model is established:80 SPF male wistar rats,20 were randomly selected as the sham operation group(only coronary artery threading,no ligation),and the remaining 60 were used Ligation of the left anterior descending coronary artery,reducing the food intake,exhaustive swimming to establish a rat model of chronic heart failure after myocardial infarction.By observing the general state of the rat,combined with electrocardiogram and echocardiography(LVEF value)to determine the establishment of the rat disease model of chronic heart failure after myocardial infarction.2.2 Observe the intervention effect of Bushen Huoxue Compound on the cardiac function and myocardial fibrosis of rats with chronic heart failure after myocardial infarction:40 rats successfully modeled were divided into model group,Bushen Huoxue compound group and Captopril group according to the random number table method.Bushen Huoxue compound group intragastric administration of Bushen Huoxue compound 15.75g/(kg·d),Captopril group intragastric administration of captopril 1.125mg/(kg·d),once a day;model group and the sham operation group was given an equal volume of normal saline,once a day by gavage.Rats in each group were comprehensively evaluated cardiac function by echocardiography combined with enzyme-linked immunosorbent(ELISA)methods(NT-pro BNP);hematoxylin-eosin(HE),Masson(Masson)and Sirius scarlet staining techniques to observe the myocardial tissue pathology and the degree of myocardial fibrosis;immunohistochemical staining method to detect the changes of fibrosis-related proteins Col ?,Col ?,a-SMA.Comprehensive the above methods to complete the study on the mechanism of Bushen Huoxue compound prescription based on the theory of "intercourse between heart and kidney" to interfere with the heart function and myocardial fibrosis in chronic heart failure rats after myocardial infarction.3 Study on the mechanism of Bushen Huoxue compound regulating Wnt/?-catenin pathway to intervene myocardial fibrosis in the treatment of chronic heart failure after myocardial infarctionTo observe the regulation effect of Bushen Huoxue Compound on Wnt/?-catenin signaling pathway,and to explore the effect mechanism of its intervention on myocardial fibrosis in rats with chronic heart failure after myocardial infarction.Animal modeling and drug treatment methods are the same as above.The collected serum and myocardial tissue samples were collected by ELISA,Western blot,Real-time PCR and other technologies to collect relevant data,and compare the protein and mRNA expression levels of key molecules Wnt/?-catenin signaling pathway Wnt3a,Dvll,?-catenin,and the changes of downstream target genes MMP-2 and MMP-9 mRNA.To observe the mechanism of Bushen Huoxue compound regulating Wnt/?-catenin pathway to interfere with myocardial fibrosis in rats with chronic heart failure after myocardial infarction.Result:1 Meta-analysis of the clinical efficacy of the method of Bushen Huoxue compound combined with western medicine in the treatment of chronic heart failure.According to the inclusion and exclusion criteria,10 randomized controlled trials were finally included for Meta analysis,and a total of 982 study patients were included.Among them,the experimental group:the method of Bushen Huoxue compound with the conventional treatment of western medicine,a total of 493 patients;the control group:the conventional treatment of western medicine,a total of 489 Cases of patients.Meta-analysis results show that the experimental group is better than the control group in improving clinical effectiveness[RR=1.26,95%CI(1.17,1.35),P<0.00001],and the experimental group is better than the control group in improving TCM syndromes[RR=1.20,95%CI(1.08,1.33),P=0.0009],the experimental group improved the left ventricular ejection fraction(LVEF)value of patients better than the control group[ND=7.71,950%CI(4.80,10.62),P<0.00001],The effect of increasing the 6-minute walking distance of patients in the experimental group is better than that of the control group[MD=87.64,95%CI(45.07,130.22),P<0.0001],and the experimental group is better than the control group in reducing the serum BNP level of patients[MD=-210.57,95%CI(-285.75,-135.39),P<0.00001],the experimental group reduced the left ventricular end systolic diameter(LVESD)better than the control group[MD=-8.14,95%CI(-12.54,-3.74),P=0.0003],all the differences in two group were statistically significant.However compared with the control group,the left ventricular end diastolic diameter(LVEDD)of the experimental group was not statistically different[MD=-6.02,95%CI(-12.40,-0.36),P=0.06].2 Effects of Bushen Huoxue compound on cardiac function and myocardial fibrosis in rats with chronic heart failure after myocardial infarction2.1 When the model is completed,the rat has a general state of chronic heart failure.The ECG shows ST segment elevation,T wave inversion or low level,and LVEF?45%.The above results prove that the model of chronic heart failure after myocardial infarction is successful.2.2 Compared with the sham operation group,LVEDD,LVESD,NT-pro BNP in the model group increased(P<0.05),and the values of LVEF and left ventricular axis shortening rate(LVFS)decreased(P<0.05),suggesting that the cardiac function of rats with chronic heart failure decreased;compared with the model group,the LVEDD,LVESD,NT-pro BNP of the Bushen Huoxue compound group and the captopril group were significantly reduced(P<0.05),and the LVEF and LVFS values were increased(P<0.05),suggesting that Bushen Huoxue compound can improve cardiac function to a certain extent.2.3 The results of HE staining suggest that the compound prescription of Bushen Huoxue compound can effectively improve myocardial cell necrosis,and to a certain extent improve fibrosis;the results of Masson staining suggest that Bushen Huoxue compound can inhibit the proliferation of collagen fibers and reduce the volume fraction of myocardial collagen;sirius red staining also suggests that Bushen Huoxue compound can inhibit collagen deposition and improve myocardial fibrosis.2.4 Compared with the sham operation group,the expression of fibrosis-related proteins Col?,Col ?,and ?-SMA in the myocardial tissue of the model group were up-regulated(P<0.05);Compared with the model group,the expression of Col ?,Col ? and ?-SMA protein in the myocardial tissues of the Bushen Huoxue compound group and the captopril group decreased(P<0.05);compared with the captopril group,the expression of Col ?,Col ? and ?-SMA protein in the Bushen Huoxue compound group was not statistically significant(P>0.05).Based on the above results,it is suggested that the compound prescription of Bushen Huoxue compound can inhibit myocardial fibrosis in rats with chronic heart failure after myocardial infarction.3 Study on the mechanism of Bushen Huoxue compound regulating Wnt/?-catenin signaling pathway to inhibit myocardial fibrosis in rats with chronic heart failure after myocardial infarctionCompared with the sham operation group,the expressions of Wnt3a,Dvll,?-catenin protein and mRNA,MMP-2 and MMP-9 mRNA in the model group were increased P<0.05);compared with the model group,the Wnt3a,Dvll,?-catenin protein and mRNA expressions of rats in the Bushen Huoxue compound and captopril groups decreased,and the downstream target genes MMP-2 and MMP-9 mRNA expressions were decreased(P<0.05);There was no statistically significant difference in the expression of Wnt3a,Dvll,?-catenin protein and mRNA,MMP-2 and MMP-9 mRNA between the captopril group and the Bushen Huoxue compound group(P>0.05).Conclusion:1 The results of Meta analysis suggest that the method of invigorating the kidney and promoting blood circulation combined with conventional western medicine has a definite effect in the treatment of chronic heart failure,compared with the conventional treatment of western medicine alone,it can significantly improve the clinical efficacy,improve the efficacy of TCM syndromes,increase LVEF and the 6-minute walk test distance,and reduce Plasma BNP levels,shrink LVESD and have fewer adverse reactions.However,large samples and high-quality clinical randomized controlled trials are still needed to confirm the conclusions.2 Ligation of the left anterior descending coronary artery combined with reducing the food intake and exhaustive swimming can successfully establish a rat model of chronic heart failure after myocardial infarction-3 Bushen Huoxue compound based on the theory of "intercourse between heart and kidney"can reduce the excessive deposition of collagen,reduce the levels of serum NT-proBNP in rats,and down-regulate the expression of fibrosis-related proteins Col ?,Col ? and ?-SMA.So as to inhibit myocardial fibrosis in rats with chronic heart failure after myocardial infarction,improve cardiac function,and effectively treat chronic heart failure.4 Bushen Huoxue compound can inhibit the activation of Wnt/?-catenin signaling pathway in rats with chronic heart failure after myocardial infarction,and down-regulate the expression of Wnt3a,Dvll,?-catenin protein and mRNA in the pathway,so that downstream MMP-2,MMP-9 mRNA expression level is reduced,thereby improving myocardial fibrosis,which may be molecular mechanism for the treatment of chronic heart failure. |
PDF Full Text Request