Yiqihuoxue Governance Act To Promote Ischemic Myocardial Angiogenesis Experimental Study And Evaluation Of Efficacy

Angiogenesis has been a tropical research in medical domain of the world. Stimulating revascularization in ischemic myocardium is a novel therapeutic strategy. Excellent clinical effect and theraputic rules of tonifying qi and activating blood are the gist of angiogenesis research of Chinese medicine.This study is divided into three parts: review, experimental research and clinical study.1. Review : This part includes 3 reviwes: therapeutic angiognensis and ischemic heart disease, progress study of therapeutic angiogenesis of TCM, overview study of clinical effect evaluation of TCM.2.Experimental research: This part includes 4 experiments:The 1^st experiment: Experimental study on rat model of aging and myocardial infarctionObjective: To study rat model of aging and myocardial infarction with D-galactose injection and coronary arteries ligating. Method: All Wistar rats were given intra-peritoneal injection of D-galactose 500 mg/kg·day for 6 weeks. Furthermore, left anterior descending coronary arteries were ligated to produce myocardial infarction in 16 Wistar rats. We oberserved these rats conditon, ECG, bite and sup, activity, determine blood GSH-PX activity and content of lipofuscin in heart. Result: This method not only achieved a aging model, but successfully made anmimals to be myocardial infarction. Conclusion: The compoud medol of D-galactose injection and coronary arteries ligating accords with some basic changes of aging and myocardial infarction.The 2^nd experiment: Stimulating angiogenesis effect of Angelicae Sinensis Decoction for Supplementing Blood on the hearts of aging and myocardial infarction ratsObjective: To study the stimulating angiogenes effect and mechanism of Angelicae Sinensis Decoction for Supplementing Blood on coronary collateral development in the hearts of experimental myocardial infarction and aging rats. Methods: All Wistar rats were given intra-peritoneal injection of D-galactose 500 mg/kg/day for 6 weeks. Furthermore, left anterior descending coronary arteries were ligated to produce myocardial infarction in 64 Wistar rats. After 2 weeks, some indexes including infarct size , expression amount of VEGF, Ⅷ-related antigen and hypoxia inducing factor-1α , serum VEGF volum were observed. Result: Angelicae Sinensis Decoction for Supplementing Blood could increase blood vessel density and expression amount of VEGF and HIF-1α , improve serum VEGF volum. These effects were similar with β -blocker. Among these treatments, middle and small dose treatment groups were better.Conclusions: Angelicae Sinensis Decoction for Supplementing Blood Pills could stimulate angiogenesis of the collateral branch of coronary artery in ischemic myocardium of aging rats and showed good protection on myocardial ischemia.The 3rd experiment: Effect of the Angelicae Sinensis Decoction for Supplementing Blood on signal transduction pathwayObjective: To study the effect of the Angelicae Sinensis Decoction for Supplementing Blood on signal transduction pathway. Method: To analyze the protein expression of PI3K and AKT of ischemic myocardial with western-blotting method. Result: Angelicae Sinensis Decoction for Supplementing Blood can improve the protein expression of PI3K and AKT. Conclusion: Angelicae Sinensis Decoction for Supplementing Blood can induce downstream protein expression of AKT by activating PI3K. And the signal is passed into cellular nucleus, introducing the expression of VEGF mRNA.The 4th experiment: Effect of serum containing expression of VEGF receptor on cultured endothelial cellObjective: To study effect of serum containing Angelicae Sinensis Decoction for Supplementing Blood on expression of VEGF receptor in cultured endothelial cell. Method: The cultured HUVEC were devided into 6 groups: control;10Qamol/L H2O2 group;bFGF+10Qumol/L H2O2 group;large dose+lOQamol/L H2O2 group;middle dose + lOQumol/L H2O2 group;small dose + 10Qamol/L H2O2 group. Immunofluorescence was used to detect HUVEC VEGF receptor, and RT-PCR was used to evaluate VEGF mRNA expression. Results: H2O2 can successfully produce hypoxia. Contrasting to control group, every dose groups all can improve expression of VEGF receptors, and middle dose and small dose have a markedly effect of up-regulating receptor. With expression of VEGFmRNA, H2O2 hypoxia group, middle dose + lOQwmol/L H2O2 group and small dose + lOOjamol/L H2O2 group have an significantly improvement. Conclusion: H2O2 can make a good chemical injury model of HUVEC. Angelicae Sinensis Decoction for Supplementing Blood of tonifying qi and activating blood can up-regulate VEGF receptor, improve the expression of VEGF mRNA, and promote angiogenesis.3. Clinical study: Chinese Medicine of Tonifying Qi and Activating Blood for acute myocardial infarction: a systematic reviewObjective: To systematically analyze the effect of Chinese Medicine of Tonifying Qi and Activating Blood on acute myocardial infarction. Methods: ?Search items were [Title: myocardial infarction] AND [ All field: (Chinese medicine) OR (Chinese herb) OR (Integrated Traditional and Western Medicine ) ] AND [All field: (Tonifying Qi) OR (Activating Blood )], the search was applied to the CBM database (1979.1 2005.12). ?Literature bolting was performed by 2 reviewers independently accordingto the standard of in and out, different opinions should be solved through negotiation. ?The relation data of literature were extracted and evaluated. ?A meta analysis was performed based on qualified literatures. Result: ?130 literatures were found out. (2) Through twice blotting, there were 42 clinical study literatures meet the evaluate procedure. ?According to the principle of modern clinical epidemiology, there were many questions of the clinical study on the treatment of AMI by TCM. The first question was lack of standards, including diagnosis and effectiveness standard. The second, there were many obviously defects on the designation, especially in randomization, blinding and statistics method. The third, the choice of observed index was not perfect, lacked of long-term indexes. The literatures mentioned about "randomize" were evaluated according to Jadad score. The evaluation of non-randomized controlled trial was also not satisfactory, no study is over 5 score. ?Only 6 literatures came into meta analysis (592 cases), the result of analysis showed that compared with basic Western Medicine drug, additional use of Chinese Medicine could not reduce E/A and LVEDd, but improve EF value and CO value, and total effective rate is also higher than basic western medicine. Conclusion: There are many questions of clinical study on the treatment of AMI by Chinese Medicine of Tonifying Qi and Activating Blood, which weaken the reliability of these studies. Meta analysis shows that Chinese Medicine of tonifying qi and activating blood has some benefits in raising left ventricular ejection fraction, cardiac minute output and total effective rate. But we can not make a final conclusion of the effectiveness of Chinese herb of tonifying qi and activating blood for AMI based on this meta-analysis.