梗阻性黄疸大鼠肾脏缺血再灌注损伤中热休克蛋白70的表达

Expression of heat-shock protein 70 in kidney after renal ischemic reperfusion injury in rats with obstructive jaundice

目的 探讨梗阻性黄疸大鼠在短暂性肾缺血再灌注过程中肾功能改变与脂质过氧化反应及大鼠肾脏热休克蛋白 70 (Heat shockprotein 70 ,HSP70 )表达之间的关系。方法 实验大鼠分为正常对照组 (S组 )、正常肾缺血再灌注组(SRI组 )、梗阻性黄疸组 (J组 )、梗阻性黄疸肾缺血再灌注组 (JRI组 )。在胆道梗阻 1周后行双侧肾动脉夹闭 10min后放开 ,观察再灌注后 0、4、12、2 4h等不同时相点观察肾功能的变化 ,采用免疫组织化学SP法观察大鼠肾脏HSP70的表达。结果 梗阻性黄疸肾缺血再灌注组内生肌酐清除率随再灌注时间延长呈持续性下降 ,梗阻性黄疸组及梗阻性黄疸肾缺血再灌注组肾组织丙二醛明显升高而超氧化物歧化酶含量下降。JRI组大鼠肾脏HSP70表达主要分布于肾近曲小管上皮细胞胞浆中 ,其表达量以再灌注后 4h最多 ,12h次之 ,2 4h有所减少。结论 梗阻性黄疸状态下大鼠肾脏对缺血再灌注损伤的敏感性明显升高 ,缺血再灌注损伤可能与梗阻性黄疸术后急性肾功能衰竭的发生有关 ,脂质过氧化反应参与了这一过程。HSP70的表达是机体对梗阻性黄祖肾缺血再灌注损伤的一种保护性反应。

Objective To illustrate the relationship between the temporary alteration of renal functions of rats with obstructive jaundice due to ischemia reperfusion injury(RI) and lipid peroxidation and the expression of heat shock protein 70 in rat kidney. Methods Wistar rats were divided into 4 groups of sham operation group(S group), sham operation and renal RI group(SRI group), common bile duct ligation group(J group), common bile duct ligation and renal RI group(JRI group). One week after bile duct ligation, rat bilateral renal arteries were transiently occluded for 10 minutes. The variations of renal function were observed at different time phases after renal reperfusion. Simultaneously, the expression of heat shock protein 70 in kidney was evaluated by immunohistochemistry. Results In JRI group, endogenous creatinine clearance rate(Ccr) decreased progressively along with the prolongation of the duration of reperfusion. In J and JRI groups, the level of malondealdehyde(MDA) in renal tissue increased but superoxide dismutase(SOD) decreased. In JRI group, the expression of heat shock protein 70 reached its peak at the 4th hour after reperfusion and began to decrease at the 12 th hour and became lowest at the 24 th hour. No expression of HSP70 was found in other groups. Conclusion The sensitivity of rat kidneys with obstructive jaundice to ischemia reperfusion injury is significantly elevated. Ischemia reperfusion injury, as well as lipid oxidative stress, may be involved in acute renal failure(ARF) after obstructive jaundice surgery. The expression of heat shock protein 70 is a protective response to RI.