Antioxidant intervention before and during myocardial ischemia may exacerbate post-ischemic myocardial dysfunction: Relationship with endothelin-1 production

Author(s): Nie R, Zhong X, Xia Z

Abstract

Objective

To investigate the protective activity of tanshinone in a rat model of myocardial ischemia-reperfusion and determine its effect on the expression of Bcl-2 and Bax in cardiomyocytes.

Methods

We established a rat model of myocardial ischemia-reperfusion. Rats were randomly divided into blank (no surgery); saline; and low-dose (2 mg/ml), medium-dose (15 mg/ml), and high-dose (50 mg/ml) tanshinone groups. We measured heart rate and troponin (cTnI) levels, performed TUNEL to detect cardiomyocyte apoptosis, and detected LDH and CK-MB activities in serum by ELISA. We performed RT-qPCR and western blot to detect the expression of Bcl-2 and Bax mRNA and protein in cardiomyocytes.

Results

Rats treated with tanshinone experienced more stable heart rate after ischemia-reperfusion compared with those in the saline control group. cTnI decreased after ischemia-reperfusion in mice injected with tanshinone, while cTnI in saline-treated mice increased significantly compared with that in the blank control group. TUNEL staining showed that there were greater apoptotic cardiomyocytes in the saline group, but the tanshinone groups showed fewer apoptotic cardiomyocytes. LDH and CK-MB activities were significantly increased after reperfusion in the saline group (p<0.01) and also in the low- and medium-dose tanshinone groups (p<0.05). However, no significant differences were found in the high-dose tanshinone group (p>0.05). The expression levels of Bcl-2 mRNA and protein in cardiomyocytes of rats were higher in the three tanshinone groups in a dose-sensitive manner than those in the blank and saline groups (p<0.05). By contrast, the expression levels of Bax mRNA and protein were reduced in the three tanshinone groups in a dose-sensitive manner compared to those in the blank and saline groups (p<0.05).

Conclusion

Tanshinone shows a protective effect in a dose-dependent manner in a rat model of myocardial ischemia-reperfusion, suggesting its potential therapeutic use.

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