内皮素-1对大鼠肾下腹主动脉阻断再灌注肾损伤实验研究

Experimental study on the effect of endothelin-1 on kidney injury caused by infrarenal abdominal aorta occlusion ischemia/reperfusion in rat model

目的:探讨内皮素-1(ET-1)对大鼠肾下腹主动脉阻断再灌注肾损伤的影响及其作用机制。方法:Wistar大鼠42只,随机分为对照组、缺血5h组、缺血5h分别再灌注2、4、8、12h组,每组7只。检测血清及肾组织匀浆内皮素-1和血浆BUN、CR水平,采用电镜观察各组大鼠肾脏及下肢肌肉形态学变化。结果:缺血及再灌注各组大鼠血清、肾组织匀浆ET-1含量较对照组高,差异有统计学意义(P<0.05),ET-1水平在I/R4h组达到最高,随后下降;各组大鼠血浆BUN水平较对照组高,差异有统计学意义(P<0.05),在I/R4h组达到最高,随后下降;各组间血浆CR差异无统计学意义。I/R4h组肾组织电镜可见肾小管核形不规则,异染色质团块边集,线粒体空泡变,内质网扩张。I/R4h组下肢肌肉组织电镜可见线粒体空泡变,肌膜不平整,肌节排列不齐。结论:大鼠肾下腹主动脉阻断再灌注可造成肾功能损伤,与缺血再灌注所激发的自由基、炎症反应、细胞内钙超载导致ET-1合成及释放增多有关。

Objective:To study the effects of endothelin-1(ET-1)on kidney injury caused by infrarenal abdominal aorta occlusion ischemia/reperfusion in rat model and its possible mechanism.Method:Forty-two healthy Wister rats were randomly divided into 6 groups as following(n=7):the control group(sham group);simply ischemia 5h without reperfusion(I group);2 hour reperfusion following ischemia 5h(I/R2h),4 hours reperfusion following ischemia 5h(I/R4h),8 hours reperfusion following ischemia 5h(I/R8h)and 12 hours reperfusion following ischemia 5h(I/R12h).In each group the rats were killed to obtain samples of blood and kidney at the specified time points.The contents of ET-1,BUN,CR in blood and in kidney were observed in each group.By electron microscope,observe the morphological changes of kidney and muscles of lower limb.Results:ET-1 level of serum and renal homogenate in model I group,I/R2h,I/R4h,I/R8h,I/R12h groups was higher obviously than control group,which were maximal in I/R4h group,then decreased.The plasma of BUN I group,I/R2h,I/R4h,I/R12h was higher obviously than control group,which were maximal in I/R4h,then decreased.Electron microscope:The injury degree of kidney and muscles of lower limb in ischemia group was slight,the injury degree of reperfusion was more severe than ischemia group.Conclusion:infrarenal abdominal aorta occlusion ischemia/reperfusion induce kidney injury in rat model,increase the level of ET-1 after ischemia-reperfusion injury of lower limbs might be concerned with the increase of ROS,inflammatory response,and intracellular Ca\{2+\} overload.