辛伐他汀对大鼠肾缺血再灌注损伤后心肌组织p53和caspase-3蛋白表达的影响

摘要

目的 观察辛伐他汀对肾缺血再灌注损伤后心肌组织的影响及其可能机制.方法 健康雄性SD大鼠36只随机分为3组(每组各12只):①假手术组(Sham);②肾缺血再灌注组(I/R);③辛伐他汀组(Sim).分组后辛伐他汀组20 mg/kg/d的辛伐他汀灌胃, 持续2周, 假手术组和肾缺血再灌注组每天给同量的生理盐水灌胃.2周后复制肾缺血再灌注损失模型.10%水合氯醛腹腔麻醉, 打开腹腔, 暴露双侧肾动静脉, 肾缺血再灌注组和辛伐他汀组夹闭双侧肾动静脉, 45 min后去夹恢复血流, 然后再逐层缝合腹壁, 假手术组开腹但不夹闭血管, 其余相同.再灌24 h后各组分别腹主动脉取血, 摘取心脏.检测血清肌酐(Scr)、尿素氮(BUN)及心肌组织丙二醛(MDA)含量, 乳酸脱氢酶(LDH)、肌酸激酶(CK)和超氧化物歧化酶(SOD)的活性,Western blot 法检测p53和caspase-3的蛋白表达水平.结果 与假手术组比, 肾缺血再灌注组Scr、BUN、MDA含量均升高(P<0.05), LDH和CK活性增强(P<0.05), SOD活性明显下降(P<0.05).与肾缺血再灌注组比较, 辛伐他汀组SCr、BUN和MDA的含量均降低(P<0.05), LDH和CK活性均明显减弱(P<0.05), 而SOD活性增强(P<0.05).与假手术组比较, p53和caspase-3蛋白表达水平在肾缺血再灌注组增多,与肾缺血再灌注组相比, p53和caspase-3蛋白表达在辛伐他汀组明显降低.结论 辛伐他汀对肾缺血再灌后心肌有保护作用, 保护机制与辛伐他汀可以消除自由基, 降低p53和caspase-3 蛋白表达有一定关系.%Objective To observe the effect of simvastatin on the apoptosis of myocardial tissue after renal ischemia-reperfusion injury in rats. Methods a total of 36 healthy male SD rats were randomly divided into 3 groups: ① sham operated group; ② renal ischemia reperfusion group; ③ simvastatin group. The simvastatin group were administered 20 mg/kg/d of simvastatin for 2 weeks, the sham and ischemic groups were administered the same amount of saline every day. After 2 weeks, the model of renal ischemia-reperfusion injury was duplicated. First of all, 10% chloral hydrate was used for intraperitoneal anesthesia. Then the abdominal cavity was opened and the bilateral renal arteries and veins were clamped in renal ischemia reperfusion group and simvastatin group. After 45 minutes, the blood flow was recovered and the abdominal wall was sutured. The sham operation group received laparotomy without vascular clamping. After 24 hours the abdominal aorta was taken from each group and the heart was removed. Creatinine (Scr), urea nitrogen (BUN) in serum, the content of malondialdehyde (MDA) in myocardium, the activity of lactate dehydrogenase (LDH), creatine kinase (CK) and superoxide dismutase (SOD) and the expression level of p53 and caspase-3 were measured. Results Compared with sham operation group, the contents of Scr, BUN and MDA in ischemic group were increased (P<0.05), the activity of LDH and CK were increased (P<0.05), and the activity of SOD was decreased (P<0.05). Compared with the ischemia reperfusion group, the content of SCr, BUN and MDA in simvastatin group were decreased (P<0.05), and the activity of SOD was increased (P<0.05). The activity of LDH and CK were decreased (P<0.05). Compared with the sham operated group, expression of p53 and caspase-3 were increased in the renal ischemia reperfusion group than those in sham operated group and simvastatin group. Conclusion Simvastatin has a protective effect on myocardial ischemia reperfusion injury in rats, and the protective mechanism may be related to the elimination of free radicals by simvastatin and reduce the expression of p53 and caspase-3 protein.