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生中的作用。大鼠右肾切除(NX)和假肾切除(Sham-NX)分别阻断左肾动脉60min，造成缺血性急性肾功能衰竭。两组均可观察到以凋亡小体和DNA片段化为特征的凋亡细胞，提示缺血肾小管上皮细胞可被诱导凋亡。NX组大鼠肾小管缺血性损伤程度明显低于Sham-NX组。肾小管损伤程度越轻，肾小管细胞凋亡率越低。用醋酸铀酰(UA)诱导大鼠肾毒性急性肾功能衰竭。UA引起大鼠血浆肌酐升高，肾小管损伤在UA后第5天达到高峰，第14天恢复到基础水平。与首次应用UA相比，UA在第14天恢复的大鼠血浆肌酐升高较少，肾小管损伤较轻，肾小管损伤减轻与肾小管细胞凋亡减少有关。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的发生发展中所起的作用。用增殖细胞核抗原阳性细胞数来评价肾小管再生的增加与肾小管损伤程度的减轻有关。相反，尿酸诱导的急性肾衰肾小管损伤程度越轻，BrdU阳性的有丝分裂细胞数越少。缺血性和肾毒性ARF之间的差异可能是由于损伤程度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.