Mechanism of Qishen Liuwei Formula in Inhibiting Endothelial-mesenchymal Transition to Improve Myocardial Fibrosis in Spontaneously Hypertensive Rats
Objective:To investigate the effect and mechanism of Qishen Liuwei Formula on myocardial fibrosis in spontaneously hypertensive rats.Methods:The spontaneously hypertensive rat(SHR)model was used,and the rats were divided into model group,low concentration group,high concentration group and Western medicine group,and Wistar-Kyoto(WKY)rats of the same age were used as control group,with 6 rats in each group.After 12 weeks of intervention,the cardiac function was monitored,and systolic function index such as left ventricular ejection fraction(LVEF),left ventricular short axis shortening rate(LVFS),and diastolic function index(early diastolic blood flow velocity(E)and mitral ring motion amplitude(E')were calculated.After 12 weeks of intervention,the rats were executed,the left ventricular myocardial tissue was extracted,and the total area of collagen fibers in the myocardium and the area of type Ⅰ collagen and type Ⅲ collagen were observed by picrate scarlet staining,and the ratio of the two collagen areas was calculated.Western Blot analysis was performed to detect the fibrination-related indexes type Ⅰ collagen,type Ⅲ collagen,matrix metalloproteinase 9(MMP-9),matrix metalloproteinase inhibitor 1(TIMP-1),endothelial-mesenchymal transition(EndMT)-associated platelet-vascular endothelial adhesion molecule(CD31),vascular endothelial-calcium-adhesion protein(VE-Cadherin),α-smooth muscle actin(α-SMA),human fibroblast specific protein 1(FSP1).The mRNA levels of CD31,VE-Cadherin,α-SMA and FSP1 of EndMT were detected by Real-time fluorescence quantification(qPCR).Result:After 12 weeks of intervention,compared with the control group,the expression of MMP-9 protein of myocardial tissue deceased in the traditional Chinese medicine group(P<0.05),the levels of myocardial interstitial type Ⅰ collagen and type Ⅲ collagen deceased(P<0.01),the diastolic function E/E'of rat heart improved(P<0.01),and the protein levels of EndMT-related proteinsα-SMA,FSP1 and the mRNA levels of VE-Cadherin,α-SMA mRNA deceased(P<0.05 or P<0.01).Conclusion:Qishen Liuwei Formula could reduce the degree of myocardial fibrosis and improve the diastolic function in SHR rats,and its mechanism might be related to the inhibition of EndMT.
hypertensionQishen Liuwei Formulamyocardial fibrosisendothelium-mesenchymal transitionmechanismqi and bloodexperimental study
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