Cardioprotective effect of San-Huang-Xie-Xin-Tang on myocardial apoptosis in ischemia-reperfusion injury

• Main Authors: Hung-Jen Ke, 柯閎仁
• Other Authors: Jwu-Lai Yeh
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/36008663266881929085

碩士 === 高雄醫學大學 === 藥理學研究所 === 96 === San-Huang-Xie-Xin-Tang (SHXT) is a Chinese medicinal formula containing Coptidis rhizoma, Scutellariae radix, and Rhei rhizome, has been used to treat gastric inflammatory diseases. However, whether SHXT has a cardioprotective effect against ischemia/reperfusion (I/R) injury remains unknown. The aim of this study was to investigate cardioprotective effects of SHXT both in an in vivo model of I/R-induced myocardial apoptosis and an in vitro model of hypoxia/reoxygenation (H/R)-induced H9c2 rat cardiomyocytes apoptosis. From in vitro and in vivo studies, our results suggested that SHXT attenuated the I/R-induced cardiac apoptosis. In a rat model of acute myocardial infarction induced by I/R, administration of SHXT inhibited I/R-induced apoptosis, as detected by ladder-pattern fragmentation of genomic DNA. SHXT improved parameters of cardiac function and hemodynamics and decreased the incidence of ventricular arrhythmia. In addition, SHXT reduced myocardial infarct size and serum levels of LDH, CK-MB, and troponin I. SHXT also increased the production of plasma NO. Furthermore, in cultured H9c2 cells, as revealed by MTT assay, treatment with SHXT prior to H/R exposure significantly increased cell viability. Suppression of hypoxia-induced apoptotic events including Hoechst 33342 staining, annexin V/PI labeling, and activation of caspases-3 by SHXT was identified in H9c2 cells. SHXT also blocked the accumulation of reactive oxygen species (ROS) and the reduction of NO induced by hypoxia. These effects of SHXT were associated with increased Bcl-2/Bax and eNOS expression and decreased ERK1/2, p38, and JNK activation. In conclusion, these results suggest that SHXT with antiarrhythmic activity may protect cardiomyocytes from I/R-induced apoptosis by scavenging free radicals and regulating the protein expression of Bcl-2 family, eNOS, and MAPK family. Thus, SHXT will be useful clinically in the prevention of acute myocardial infarction.