氟伐他汀对大鼠肾缺血再灌注损伤P27和PCNA表达的影响

目的:探讨大鼠肾缺血再灌注损伤(renal ischaemia reperfusion injury,IRI)中细胞周期抑制蛋白P27和增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)在肾小管上皮细胞中的表达及氟伐他汀(fluvastatin)对P27和PCNA表达的影响。方法:将30只大鼠随机分为3组,假手术组(sham组)10只;IRI组即对照组10只;Fluvastatin治疗组(Flu组)10只。术前3d给予Fluvastatin(2mg/kg)灌胃。造成缺血再灌注肾病模型,术后24h处死大鼠,取肾脏做组织学检查,检测P27和PCNA在肾组织内表达的部位、程度。结果:组织学检查发现Flu组较IRI组形态学变化有所减轻。细胞增殖指数(Cell Proliferative Index,PI)以IRI组增殖最明显,Flu组与之比较有统计学意义。免疫组化结果显示sham组P27表达程度最高,IRI组P27水平降低,Flu组P27表达水平复又升高,与IRI组比较(P<0.01)。相关分析:肾小管评分与PI成正相关(r=0.872,P<0.01);肾小管评分与P27成负相关(P=-0.713,P<0.01);PCNA和P27的表达呈负相关(P=-0.609,P<0.01)。结论:肾缺血再灌注24h后P27水平下降和PCNA水平升高,氟伐他汀可以进一步增强P27的表达,并使PCNA的表达受到抑制,使细胞周期停滞,有助于受损的肾小管上皮细胞DNA的修复,从而发挥肾保护作用。

Effect of fluvastatin on expression of P27 and PCNA in renal Ischemia/reperfusion model of rats

Objective To investigate the expressions of P27 and PCNA on renal tubular epithelial cells in renal ischaemia and reperfusion injury,and evaluate the effect and possible mechanism of HMG-COA reductase inhibiter fluvastatin on expressions of P27 and PCNA in the cells. Methods 30 rats were randomly divided into 3 groups: sham-operated group(n = 10); IRI group (n = 10); fluvastatin treatment group (n = 10). The in vivo study was conducted by establishing rat model of acute ischemic renal failure through ischae...