Li He, Wang Chunmei, Sun Jinghui, Liu Cong, Li Ning, Chen Jianguang
Department of Pharmacology, Pharmaceutical College, Beihua University.
Int Heart J. 2018;59(1):154-160. doi: 10.1536/ihj.16-607.
Our previous study showed that pravastatin prevents ischemia and reperfusion-induced lethal ventricular fibrillation in rats. This study explored whether pravastatin decreases myocardial infarct size and this effect is associated with endothelial nitric oxide synthase (eNOS) expression in myocardium. Rats were treated with ischemia (30 minutes) and reperfusion (60 minutes) after chronic oral administration of pravastatin, fluvastatin, or vehicle once daily for 22 days. Electrocardiograms and blood pressure were continuously recorded, myocardial infarct size was measured by TTC-staining, and eNOS expression was measured by western blot. The results showed that pravastatin and fluvastatin significantly reduced myocardial infarct size. No statistical differences were found in the areas at risk among all groups. However, a significant reduction in infarct size was observed in three pravastatin groups and one fluvastatin group compared to control. Both pravastatin and fluvastatin significantly increased eNOS protein expression in ischemic and non-ischemic tissues compared to control. Our results suggest that pravastatin decreases cardiovascular mortality beyond its cholesterol-lowering effect. Pravastatin is more potent than fluvastatin in reducing infarct size. These effects may be associated with elevation of eNOS expression.
我们之前的研究表明,普伐他汀可预防大鼠缺血再灌注诱导的致死性室颤。本研究探讨了普伐他汀是否能减小心肌梗死面积,以及这种作用是否与心肌中内皮型一氧化氮合酶(eNOS)的表达有关。大鼠连续22天每日口服一次普伐他汀、氟伐他汀或赋形剂,随后进行缺血(30分钟)和再灌注(60分钟)处理。连续记录心电图和血压,通过TTC染色测量心肌梗死面积,通过蛋白质免疫印迹法测量eNOS表达。结果显示,普伐他汀和氟伐他汀均显著减小了心肌梗死面积。所有组之间的危险区域未发现统计学差异。然而,与对照组相比,三个普伐他汀组和一个氟伐他汀组的梗死面积显著减小。与对照组相比,普伐他汀和氟伐他汀均显著增加了缺血和非缺血组织中eNOS蛋白的表达。我们的结果表明,普伐他汀降低心血管死亡率的作用超出了其降胆固醇作用。在减小梗死面积方面,普伐他汀比氟伐他汀更有效。这些作用可能与eNOS表达升高有关。