Effect of simvastatin on pro-inflammatory cytokines after myocardial in farction in rats

Objective: To study the effect of simv astatin on mRNA expression of inflammatory cytokines, including TNF-α, IL-1β, IL-6, and IL-10, after myocardial infarction (MI) in rats. Methods: The experimental rats were di vided into three groups: Sham operation group (Sham), the rats were performed a left thoracotomy with no ligation of left descending coronary artery (LAD); Myoc ardial infarction control group (MI-C), the rats were performed a left thoracot omy with ligation of LAD; Simvastatin group (MI-S), the rats were performed a l eft thoracotomy with ligation of LAD, and given simvastatin 40 mg/kg body weight per day through gavage, while the other two groups were given equal normal sali ne by gavage. All animals were caged to feed four weeks. After finished, the rat s were killed, and the hearts were harvested and cut into two equal parts at the level of the papillary muscle: one was used to determine mRNA expression of myo cardial cytokines by RT-PCR, and the other was used to measure cytokines by Wes tern blotting and immunohistochemical staining. Results: All the pro-inflammatory cytokines mentioned above showed few expression in Sham opera tion group. In the MI groups (including MI-C and MI-S groups), mRNA expression of each of these cytokines markedly increased compared with the Sham operation group (P<0.01). Compared with MI-C group, the mRNA expression of TNF- α, IL-1β and IL-6 in the MI-S group significant ly reduced (P<0.01), and mRNA expression of IL-10 obviously increased ( P<0.01). Cytokines principally located in cardiomyocytes of non-infarcted ar ea and survived cardiomyocytes of infarcted area, simvastatin could decrease TNF -α, IL-1β, and IL-6 and increase IL-10 by confirmation of immunohistochemical staining. Conclusion: Simvas tatin markedly lowers pro-inflammatory cytokines, and increases inflammatory pr otective cytokine. Its mechanism needs to be elucidated.