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

الملخص EN

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.