HSP70和NF-κB在大鼠肾缺血再灌注损伤中的表达及洛伐他汀的干预研究

摘要

目的 探讨洛伐他汀(Lovastatin,Lov)对大鼠肾缺血再灌注损伤(RIRI)热休克蛋白70 (HSP70)和核因子-κB (NF-κB)表达的影响.方法 90只Wistar大鼠随机分为3组:假手术(Sham)组、缺血再灌注模型(IR)组、洛伐他汀(Lov)组.IR组和Lov组大鼠采用夹闭肾动脉60 min后再灌注的方法制备RIRI模型,Lov组于动脉夹闭前给予洛伐他汀2mg/(kg·d)灌胃,各组大鼠在再灌注4、12、24 h时分别处死10只取标本.测定各组大鼠的血肌酐(Scr)、尿素氮(BUN)水平,免疫组化法检测肾组织HSP70和NF-κB表达,镜下观察肾组织形态学改变.结果 与Sham组大鼠相比,IR组大鼠在再灌注4、12、24 h时点的Scr和BUN含量均显著升高；肾组织HSP70和NF-κB表达均明显增强,差异均有统计学意义(P均＜0.05).与IR组相比,Lov组大鼠在各时点的Scr和BUN含量均显著降低(P均＜0.01)；HSP70表达均升高(P均＜0.05)；NF-κB表达减少,再灌注4、12 h时,两者差异有统计学意义(P＜0.05)；镜下病理改变减轻.结论 Lov可通过增加肾脏HSP70、下调NF-κB达而抑制炎症反应过程,减轻肾脏损害,对大鼠RIRI起到一定的保护作用.%Objective To investigate the possible effects of Lovastatin on the expression of HSP70 and NF-KB in rats after renal ischemia-reperfusion injury (RIRI). Methods Ninety Wistar rats were randomly divided into 3 groups, sham-operated group, IR group and Lov group. The model of RIRI in IR and Lov groups was established by the clamping of the kidney artery for 60 minutes. Lovastatin was given 2mg/(kg·d) by oral gavage to the rats in the Lov group before clamping of the kidney artery. Ten rats in each group were executed at 4, 12, and 24 hours after reperfusion. The concentrations of serum creatinine (Cr) and urea nitrogen (BUN) were detected, and the expression of HSP70 and NF-KB in renal tissues was detected by immunohistochemistry. The pathologic changes of renal tissues were observed by microscope. Results At 4, 12, and 24 hours after reperfusion, compared with sham-operated group, serum Cr and BUN were significantly increased in rats of IR group (PO.01), and the expression of HSP70 and NF-KB in renal tissues was also enhanced (P＞＜0.05). Compared with IR groups, in Lov group serum Cr and BUN were significantly decreased at different time points after reperfusion (P＜0.01); the expression of HSP70 in renal tissues was increased (P＜0.05); the expression of NF-KB was decreased and the difference was significant at 4 h, 12 h after reperfusion (P＜0.05). Furthermore, the renal histological injury was alleviated in Lov rats. Conclusion Lovastatin which suppresses the inflammatory reaction through up-regulating the expression of HSP70 and meanwhile down-regulating the expression of NF-KB may have protective effects to some extent on renal injury in RIRI rats.