大鼠急性肾损伤导致肝细胞凋亡的实验研究

 目的：观察大鼠急性肾损伤（AKI）引起肝细胞凋亡的细胞学特点。方法：建立AKI（包括缺血性和非缺血性）大鼠模型后应用免疫印迹法、免疫组织化学染色法和光学、电子显微镜技术对AKI大鼠的肾脏和肝脏进行观察。结果：(1) 缺血性AKI 肾小管出现了大面积细胞坏死和细胞凋亡的表现。不论是缺血性还是非缺血性AKI的动物都发生了急性肾功能损伤和急性肝功能受损。(2) 免疫印迹法测定结果显示AKI动物肝脏的肿瘤坏死因子受体α（TNFRα）和半胱氨酸天冬氨酸蛋白酶-3（caspase-3）蛋白表达增强。从caspase-3免疫组化染色的结果可以看出阳性细胞均出现在AKI动物肝脏内。(3) 电子显微镜观察发现AKI动物肝脏中确有细胞凋亡和副凋亡的表现。(4) 缺血性与非缺血性AKI诱导肝细胞凋亡的表现相同。结论：AKI可引起肝细胞凋亡和副凋亡，其中经TNFRα启动的caspase依赖的细胞死亡构成了AKI引起的肝细胞凋亡。这种肝细胞凋亡是由肾功能损伤导致的血尿毒物质引起的。

Apoptosis of hepatocytes induced by acute kidney injury in rats

AIM: To observe the cytological changes of hepatocytes undergoing apoptosis induced by acute kidney injury (AKI) in rats. METHODS: The rat models of AKI, including ischemic and non-ischemic AKI, were established. Western blotting, immunohistochemical staining, light and electron microscopy were used in this study. RESULTS: Cellular necrosis in renal tubules, as the basic morphological changes of ischemic AKI, and renal tubular cells undergoing apoptosis were evident in ischemic AKI. Meanwhile, tumor necrosis facotor receptor α (TNFRα) and caspase-3 was strongly expressed in the livers from AKI rats. Caspase-3-positive cells were evident in the livers from AKI rats. Microscopic examinations revealed that hepatocytes undergoing apoptosis and para-apoptosis were observed in damaged livers of both ischemic and non-ischemic AKI animals. No significant difference of hepatic apoptosis between ischemic and non-ischemic AKI animals was observed. CONCLUSION: Either apoptosis, caspase-dependent cell death or para-apoptosis are involved in hepatic injury induced by AKI. TNFRα initiation and cleaved caspase family are the pathways of hepatocytes undergoing apoptosis induced by AKI.