To Explore The Effect And Mechanism Of ASHRP On RIHD Based On The Theory Of Yiqihuoxue

Objective: To evaluate the clinical efficacy of conventional therapy combined with Yiqi Huoxue Recipe in the treatment of chronic heart failure(CHF)based on meta-analysis.To investigate the pathogenesis of radiation-induced heart disease(RIHD)in vitro experiments on H9C2 cell and demonstrates the intervention mechanism of angelica sinensis and hedysari radix polysaccharide treat for RIHD that can provides a theoretical basis for the early prevention of CHF.Method: Meta-analysis of the clinical efficacy of Yiqi Huoxue Recipe in the treatment of CHF: 1.Develop a search strategy,formulate inclusion and exclusion criteria,set outcome indicators and performing the literature search.2.According to the inclusion and exclusion criteria,quality assessment and Cochrane Review Manual 5.3.0 to comprehensively evaluated the literature,and the literatures were performed using RevMan 5.3 software.Experimental research methods: 1.After the cell culture,the changes of cell morphology and the cell viability was measured for establishment of a cell model.2.To determine the relationship between oxidative stress and activation of Rho/Rock pathway: Elisa assay was used to detect the expression of oxidative stress indicators such as SOD,MDA and GSH,and the method of Western blot and RT-PCR were used to detect iNOS,eNOS,Rhoa and Rock.,MYPT-1,JNK protein and its corresponding mRNA expression,thereby clarifying the occurrence of oxidative stress in RIHD and its correlation with Rho/Rock pathway activation,On this basis,the mechanism of the intervention of ASHRP on oxidative stress and Rho/Rock pathway activation was discussed.3.To clarify the correlation between Rho/Rock pathway activation and apoptosis,inflammatory response: detection of IL-6,IL-8,TNF-α,MCP-1,Caspase-3,Bcl-2,Bax and other inflammations by elisa,and flow cytometry was used to detect cell cycle and apoptosis.And further explore the mechanism of ASHRP regulating apoptosis and inflammation by inhibiting the activation of Rho/Rock pathway;4.To determine the correlation between apoptosis and myocardial fibrosis: Western Blot,RT-PCR method to detect the expression of ColIII,FN,LN,MMP-3 protein and its mRNA,thus revealing the correlation between apoptosis and cell fibrosis and explore the molecular mechanism of ASHRP to reverse cardiomyocyte fibrosis by reducing inflammation and apoptosis.Result: The results of meta-analysis of the efficacy of Yiqi Huoxue Recipe on CHF clinical treatment: 1.Literature search results: A total of 1715 related studies were retrieved,and 24 RCT studies were included in the study according to the inclusion exclusion criteria,finally;2.Literature quality evaluation and bias analysis: The quality evaluation results show that the quality of the 24 articles included in the study was so low,and the risk of bias was large;3.Outcome index evaluation results: conventional treatment combined with Yiqihuoxue recipe can significantly improve the 6MWT,LVEF,CO,and total effective rate of CHF patients,and can significantly reduce level in blood of BNP,NT-proBNP and MLHFQ score,Lee score,while it was certificated that Yiqihuoxue recipe was no significant effect on E/A,and the results show that Yiqi Huoxue Recipe has a significant effect on CHF treatment.Experimental results: 1.Cell morphology changes: the number of cells decreased,the volume became smaller,the adherence ability decreased,the fusiform structure changed after X-ray irradiation,and the morphological structure changed more obviously with the increasing of radiation dose;2.Decreased cell activity: the cell viability decreased by 53% compared with control group after 2Gry dose irradiation,and the cell activity decreased more with the increasing of radiation dose.Therefore,the cell model was established after 2 Gry dose irradiation.3.Oxidative stress response and activation of the Rhoa/Rock signaling pathway: compared of SOD,MDA,GSH,iNOS,eNOS,RhOA,Rock,p-MYPT-1,p-JNK proteins and mRNA expression after different interventions,indicating that Rho/Rock and downstream pathways were activated after oxidative stress in RIHD,while high dose of ASHRP can significantly interfered with oxidative stress and inhibited Rho/Rock pathway activation;4.Activation of Rhoa/Rock signaling pathway and apoptosis,inflammatory response: expression of IL-6,IL-8,TNF-α,MCP-1,Caspase-3,Bcl-2,Bax and cell cycle,apoptosis were compared in different interventions.Apoptosis was a downstream reaction of Rho/Rock pathway activation;5.Apoptosis and myocardial fibrosis: By comparing the expression of ColIII,FN and LN in different interventions,indicating that cell fibrosis was regulated by apoptosis,while ASHRP can inhibits apoptosis and reduces fibrosis.Conclusion:1.Conventional treatment combined with Yiqi Huoxue method has a significant clinical effect in the treatment of CHF.2.The possible mechanism of high-dose radiation-induced RIHD is that X-ray radiation leads to the occurrence of oxidative stress in cells,while MDA and ROS produced by oxidative stress activate Rho/Rock and its downstream pathways and induce inflammation and apoptosis,and inflammation factor,caspase-3 and other apoptotic proteins further induce myocardial fibrosis.Angelica sinensis polysaccharide can inhibit oxidative stress,Rho/Rock pathway,inflammatory reaction,apoptosis and other effects,and can reverse the occurrence of myocardial fibrosis by multiple pathways and multiple targets.