大鼠双侧肾切除后肝细胞的损伤方式

Damage modes of hepatocytes after bilateral nephrectomy in rats

目的:观察大鼠双侧肾切除[非缺血性急性肾损伤(non ischemic acute kidney injury,NIAKI)]引起肝细胞损伤方式。方法:应用Western blot、免疫组织化学染色方法和光学、电子显微镜技术对双侧肾切除24 h后的大鼠肝脏进行了观察。结果:双侧肾切除24 h后的大鼠发生了急性肝功能受损,肝脏出现了大小不等坏死灶以及大面积区域性肝细胞的空泡样改变。光、电镜观察结果证明前者以细胞坏死为主,后者以细胞内出现大量空泡为主要表现。此外尚可见少许肝细胞凋亡的表现。Western blot的结果说明双侧肾切除后肝脏内多聚ADP核糖聚合酶(polyADP-ribose polymerase,PARP)-1过度激活,肿瘤坏死因子受体1和caspase-3蛋白表达均增强。免疫组化染色结果可见双侧肾切除后肝脏内出现了PARP-1阳性和caspase-3阳性的肝细胞。结论:形态学上NIAKI可引起肝细胞坏死,肝细胞空泡化与细胞凋亡,以前2种损伤为明显。从生物化学角度可以看出PARP-1介导的细胞死亡与caspase依赖的细胞死亡参与了NIAKI引起的急性肝损伤。

Objective：To observe the morphological changes of hepatocyte injury induced by bilateral nephrectomy due to non ischemic acute kidney injury（NIAKI）. Methods：Western blot,immunohistochemical staining,light and electron microscopy were used in this observation at 24 h after bilateral nephrectomy. Results：Acute liver damage was observed at 24 h after bilateral nephrectomy. Necrotic and vacuolization lesions were predominately evident in damaged livers after nephrectomy. Besides necrosis,hepatocytes with vacuolization was also observed under electron microscopes. Meanwhile,polyADP-ribose polymerase-1（PARP-1）,tumor necrosis factor receptor 1 and caspase-3 were expressed much stronger in NIAKI associated livers by Western blot analysis. Immunohistochemical staining demonstrated that PARP-1 positive nucleuses and caspase-3 positive cells were observed in the acute hepatic injury induced by nephrectomy. Conclusion：NIAKI can induce necrosis,apoptosis and vacuolation of liver cells,more evident in necrosis and apoptosis,based on morphological observation. PARP mediated cell death and caspase-dependent cell death are involved in NIAKI associated hepatic damages.