辛伐他汀对肾缺血再灌注损伤大鼠脑组织OFR NO和NOS的影响

Effects of Simvastatin on OFR,NO and NOS in Brain Tissue of Rats with Renal Ischemia Reperfusion Injury

目的:观察辛伐他汀对肾缺血再灌注损伤后对脑组织的影响及影响机制。方法:复制肾缺血再灌注损伤(RIRI)模型(10%水合氯醛腹腔麻醉,打开腹腔,暴露双侧肾动静脉,用动脉夹夹闭双侧肾动静脉,45min后去除动脉夹恢复血流,然后再逐层缝合腹壁)。随机将36只大鼠分为3组:假手术组;肾缺血再灌注组;辛伐他汀组。每组12只。检测血清肌酐(Scr)、尿素氮(BUN)含量,检测脑组织丙二醛(MDA)含量、一氧化氮(NO)含量、超氧化物歧化酶(SOD)活性、诱导型一氧化氮合酶(iNOS)活性以及内皮型一氧化氮合酶(eNOS)的蛋白表达水平。结果:与假手术组比,缺血组血清Scr、BUN水平升高(P<0.05)脑组织MDA、NO含量以及iNOS活性均都升高(P<0.05),而SOD活性明显下降(P<0.05)。与缺血再灌注组比较,辛伐他汀组血清SCr、BUN水平降低(P<0.05)和脑组织MDA的含量降低(P<0.05),iNOS活性亦降低(P<0.05),SOD活性和NO含量增加(P<0.05)。肾缺血再灌注组eNOS蛋白含量与假手术组相比增加(P<0.05),与肾缺血再灌注损伤组相比,辛伐他汀组eNOS蛋白含量增加(P<0.05)。结论:辛伐他汀对肾缺血再灌后脑组织的损伤有一定的保护作用。其机制与辛伐他汀可以清除自由基,降低iNOS含量,提高eNOS的表达,同时增加NO含量有关。

Objective：To observe the effect of simvastatin on brain tissue after renal ischemia reperfusion injury and its mechanism.Methods： A rat model of renal ischemia reperfusion injury （RIRI） was prepared by clamping the bilateral renal arteries for 45 minutes（10% chloral hydrate intraperitoneal anesthesia, open the abdominal cavity, exposed bilateral renal artery and vein, clamping the bilateral renal artery and vein with artery clamp, 45min after removal of the artery clamp to restore blood flow, and then suture the abdominal wall）.36 rats were randomly divided into the following groups, 12 rats in each group： sham operation group;renal ischemia reperfusion group;simvastatin group.Detection of serum creatinine （Scr）, urea nitrogen （BUN）, brain tissue malondialdehyde （MDA） and nitric oxide （NO） content, superoxide dismutase （SOD） and inducible nitric oxide synthase （iNOS） activity in brain tissue was detected in endothelial nitric oxide synthase （eNOS） protein expression level.Results： Compared with the sham operation group, the contents of Scr, BUN, MDA, NO and iNOS activity in the ischemic group increased （P〈0.05）, while the activity of SOD decreased （P〈0.05）.Compared with the ischemia reperfusion group, the content of SCr, BUN and MDA decreased, iNOS activity was decreased （P〈0.05）, but the activity of SOD and the content of NO increased （P〈0.05）.The content of eNOS protein in renal ischemia reperfusion group was higher than that in sham operation group （P〈0.05）, and the content of eNOS protein in simvastatin group was higher than that in the renal ischemia reperfusion injury group （P〈0.05）.Conclusion：Simvastatin can protect the brain from ischemia reperfusion injury.It may be related to decreased the activity of iNOS, and increase the expression of eNOS protein and the content of NO.