San-Huang-Xie-Xin-Tang Prevents Rat Hearts from Ischemia/Reperfusion-Induced Apoptosis through eNOS and MAPK Pathways

 

Shu-Fen Liou, Hung-Jen Ke, Jong-Hau Hsu, Jyh-Chong Liang, Hung-Hong Lin,

Ing-Jun Chen, and Jwu-Lai Yeh

 

Abstract

---

San-Huang-Xie-Xin-Tang (SHXT) is a traditional Chinese medication consisting of three herbs, namely Coptidis rhizome, Scutellariae radix and Rhei rhizome. This study aimed to examine the cardioprotective effects of SHXT in a rat model of acute myocardial apoptosis induced by ischemia/reperfusion (I/R). Vehicle (intravenous saline) or SHXT (intravenous or oral) was administered prior to I/R (occlusion of left coronary artery for 45 min followed by reperfusion for 2 h). In the vehicle group, myocardial I/R caused myocardial infarction with increased plasma cardiac enzymes, severe arrhythmia and mortality. Myocardial apoptosis was induced by I/R as evidenced by DNA ladder and Bcl-2/Bax ratio. In the SHXT group, we found that SHXT significantly reduced plasma levels of cardiac enzymes, arrhythmia scores (from 5 ± 1 to 2 ± 1, P<.01) and mortality rate (from 53 to 0%, P<.01). In addition, pretreatment with intravenous SHXT reduced the infarct size dose-dependently when compared with the vehicle group (10 mg kg^-1: 14.0 ± 0.2 versus 44.5 ± 5.0%, and 30 mg kg^-1: 6.2 ± 1.2% versus 44.5 ± 5.0%, both P<.01). Similarly, oral administration of SHXT reduced the infarct size dose-dependently. Furthermore, SHXT markedly decreased the apoptosis induced by I/R with increased Bcl-2/Bax ratio. Finally, we found that SHXT counteracted the I/R-induced downstream signaling, resulting in increased myocardial eNOS expression and plasma nitrite, and decreased activation of ERK1/2, p38 and JNK. These data suggest that SHXT has cardioprotective effects against I/R-induced apoptosis, and that these effects are mediated, at least in part, by eNOS and MAPK pathways.

 

Copyright © 2011 Shu-Fen Liou et al. This is an open access article

distributed under the Creative Commons Attribution License,

1.              Introduction

2.              Materials and methods

1.           Materials and Reagents

2.           Experimental Animals

3.           Experimental Protocol

4.           Evaluation of Arrhythmia and Mortality

5.           Determination of Myocardial Infarct Size

6.           Measurement of Plasma LDH, CK-MB and Troponin I

7.           Determination of Plasma Nitrite Production

8.           Detection of DNA Fragmentation

9.           Western Blotting

10.       Statistical Analysis

3.              Results

1.           Ventricular Arrhythmia and Mortality Rate

2.           Myocardial Infarct Size

3.           Plasma CK-MB, LDH and Troponin I

4.           Myocardial DNA Fragmentation

5.           Myocardial Expression of Bcl-2 and Bax

6.           Myocardial eNOS Protein and Plasma NO Production

7.           MAPK Pathway

4.              Discussion

5.              Acknowledgements

6.              References

Join our member to get full-text article! Join Free!