The study on the factors which enhance the recovery from acute renal failure.

本研究的目的是评估细胞凋亡和肾小管再生在缺血性和肾毒性急性肾功能衰竭发展中的作用。右肾切除（Nx）和假肾切除（sham-Nx）大鼠左肾动脉闭塞60分钟引起缺血性急性肾衰竭。两组均观察到以凋亡小体和DNA断裂为特征的凋亡细胞，提示缺血小管细胞凋亡的诱导作用。Nx大鼠缺血性肾小管损伤明显小于假Nx大鼠。小管损伤越轻，小管细胞凋亡越少。采用醋酸铀酰（UA）注射液致肾毒性急性肾功能衰竭。UA诱导血浆肌酐升高，组织学肾小管损伤在UA后第5天达到峰值，第14天恢复到基础水平。与第一次给药相比，先前急性肾衰竭恢复的大鼠在第14天再次给药UA引起的血浆肌酐升高较小，肾小管损伤较小。再激大鼠的小管损伤程度越轻，小管细胞的凋亡也越少。这些发现提示细胞凋亡在缺血性和肾毒性急性肾功能衰竭发展中的作用。以PCNA阳性细胞数量评估的小管再生增加与缺血性ARF小管损伤较少相关。相反，在ua诱导的ARF中，小管损伤越少，与BrdU阳性的有丝分裂细胞数量越少相关。缺血ARF与肾毒性ARF的差异可能是由于损伤程度的不同或评价肾小管细胞再生的方法不同所致。

The aim of this study was to evaluate the roles of apoptosis and tubular regeneration in the development of ischemic and nephrotoxic acute renal failure. Ischemic acute renal failure was provoked by a 60-min left renal artery occlusion in right nephrectomized (Nx) and sham-nephretomized (sham-Nx)rats. Apoptotic cells characterized by apoptotic body and DNA fragmentation were observed in both groups, suggesting the induction of apoptosis in ischemic tubular cells. Ischemic tubular injury was significantly less in Nx rats than sham-Nx animals. Less tubular injury was associated with less apoptotic tubular cells. Nephrotoxic acute renal failure was induced by the injection of uranyl acetate (UA). UA-induce increase in plasma creatinine and the histological tubular injury peaked on day 5 following UA and returned to basal level on day 14. The re-administration of UA on day 14 to rats recovered from previous acute renal failure induced less increase in plasma creatinine and less tubular damage compared with the first US.Less tubular damage in rechallenged rats was associated with the less apoptotic tubular cells. These findngs suggest the role of apoptosis in the development of ischemic and nephrotoxic acute renal failure. The increased tubular regeneration evaluated with the number of PCNA positive cells was associated with the less tubular damage in ischemic ARF.In contrast, the less tubular damage in UA-induced ARF was associated with the less number of mitotic cells evaluated with positive BrdU.The discrepancy between ischemic and nephrotoxic ARF might be caused by the difference of insult or the difference of the method to evaluate the regeneration of tubular cells.