阿托伐他汀预处理通过增加内皮型一氧化氮合酶表达保护大鼠肾缺血再灌注损伤

Atorvastatin preconditioning protect renal function against ischemia-reperfusion injury by increasing expression of endothelial nitric oxide synthase

目的 观察阿托伐他汀预处理对大鼠急性肾缺血再灌注损伤的保护作用,并探讨其可能机制.方法 将18只雄性SD大鼠随机分为3组：假手术组、缺血再灌注组及阿托伐他汀组,在缺血再灌注处理前2周开始对阿托伐他汀组大鼠经腹腔注射阿托伐他汀[20 mg/（kg·d）],假手术组及缺血再灌注组同法给予等量生理盐水.分析再灌注48 h后各组大鼠血清尿素氮（BUN）、肌酐（Cr）、一氧化氮（N0）水平以及其肾脏组织中髓过氧化物酶（MPO）、内皮型一氧化氮合酶（eNOS）、超氧化物歧化酶（SOD）表达水平.结果 与缺血再灌注组比较,阿托伐他汀预处理可降低BUN（mmoL/L,78.59±10.47比128.54±6.69）及Cr（μmol/L,19.44±9.30比31.44±9.87）水平,增加NO（μmol/L,94.65±10.33比67.50±8.32）水平,减少MPO（U/g,1.25±0.14比1.68±0.12）表达,增加SOD[U/（mg·酶蛋白）,139.0±10.6比109.0±4.7]及eNOS表达,差异均有统计学意义（P＜0.05）.结论 阿托伐他汀预处理对大鼠肾缺血再灌注损伤有保护作用,作用其机制可能与eNOS的诱导合成增多,NO产生增多有关.

Objective To investigate the protective effect of atorvastatin （ATO） preconditioning on rats with acute renal ischemia-reperfusion （I/R） injury and its effect on endothelial nitric oxide synthase （eNOS）.Methods 18 male Sprague Dawley rat was randomly distributed into three groups：sham,I/R and I/R ＋ ATO.ATO was given by intraperitoneal injection [20 mg/（kg·d）] 2 weeks before ischemia/ reperfusion operation in the I/R ＋ ATO group.The sham group and I/R group received saline vehicle via the intraperitoneal route.Serum levels of blood urea nitrogen （BUN）,creatinine （Cr）,nitric oxide （NO） and expression levels of myeloperoxidase （MPO）,eNOS and superoxide dismutase （SOD） in renal tissue were analyzed.Results Comparing with the sham group,ATO treatment reduced the elevation of BUN （mmol/L） （78.59±10.47 vs.128.54 ±6.69） andCr（μmol/L） （19.44±9.3vs.31.44±9.87） level,inhibited the expression of MPO （U/g） （1.25 ±0.14 vs.1.68 ±0.12）,but increased the expression of SOD [U/（mg·pro）] （139 ± 10.6 vs.109 ±4.7）,and enhance the elevation of NO （μmol/L）（94.65 ± 10.33 vs.67.50 ±8.32） and eNOS.All differences were significant.（P 〈0.01）.Conclusion These data suggest that ATO protect renal function from ischemia-reperfusion injury probably by promote the expression of eNOS and consequently increase the production of NO.