大鼠急性肾功能衰竭时肾小管上皮细胞凋亡及其意义

Tubular epithelial cell apoptosis and its significance in acute renal failure

目的 探讨肾小管上皮细胞凋亡在急性肾功能衰竭 (acuterenalfailure ,ARF)中的意义。 方法 以体积分数为 5 0 %的甘油分别按 5ml/kg和 10ml/kg的剂量注射于Wistar大鼠后肢肌肉 ,造成不同程度的ARF ,在注射后 1,3,6 ,12 ,2 4,48,96h测定肾功能 ,并取肾脏分别以原位末端标记法 (TUNEL)、流式细胞仪 (FCM)及瑞氏染色等检测肾小管上皮细胞的凋亡。 结果 甘油注射后有肌红蛋白尿排出 ,肾功能明显受损 ,程度与甘油注射剂量有关。两实验组均可见肾小管上皮细胞凋亡 ,大剂量组较显著。肾小管上皮细胞的凋亡变化早于肾功能改变 ,且与肾功能相关。 结论 肾小管上皮细胞凋亡是ARF时肾功能障碍的组织学基础之一 ,其在ARF防治中的作用有待进一步研究。

Objective To investigate the role of tubular cell apoptosis in the development of acute renal failure (ARF). Methods ARF was induced by glycerol injection intramuscularly at different dosage in Wistar rats. At 1, 3, 6, 12, 24, 48 and 96 h after injection, the blood and kidney specimens were obtained. Then renal function was monitored by detecting Cr and BUN in serum. And specimens of kidney were made into paraffin sections. Pathological changes were observed by HE and Wright's staining and apoptosis of renal tubular epithelium cells was studied by TUNEL, FCM and Wright's staining. Results Tubular cell exfoliation, karyopyknosis, gemmation and necrosis could be seen. The damage appeared in outer medulla firstly and predominantly in proximal tubules. In high dosage group, the injuy was more serious. The most dramatic histologic changes in the kidney were found in the distal tubule of outer medulla. In both experimental groups, the apoptotic label indexes were significantly higher than the control group from 1 to 96 h and their peak value(44.53% and 31.83%, P <0.01) appeared at 24 h. LM and FCM also confirmed the presence of apoptosis. Conclusions Our results suggest that the necrosis and apoptosis are determined by the injury degree. Apoptosis of tubular cells plays an important role in mild damage of renal function. Meanwhile, necrosis and apoptosis are predominant in proximal and distal tubular, respectively, which show that the injury mechanisms of distal and proximal tubule are different.