Unilateral ureteral obstruction (UUO) results in widespread tubular apoptosis in obstructed kidneys of both adults and neonates. The oncoprotein bcl-2 inhibits many forms of apoptosis, whereas the related protein bax promotes apoptosis. To evaluate the interaction of bcl-2, bax, and apoptosis in the renal response to UUO, adult and neonatal rats were subjected to UUO or sham operation, and kidneys were harvested 14 days later. Apoptotic cells were identified by the Tunel technique, and the distribution of bcl-2 and bax was determined by immunochemistry. In both adults and neonates, tubular and interstitial apoptosis was present in the obstructed kidney, but not in intact kidneys. In both adults and neonates, there was diffuse tubular bcl-2 and bax staining of sham-operated and intact kidneys. While bcl-2 was increased in scattered nonapoptotic tubules of the obstructed kidney, there was minimal staining of dilated apoptotic tubules. These results are consistent with the premise that bcl-2 normally suppresses renal tubular apoptosis. The distribution of bax staining in tubules of the obstructed kidney overlapped that of bcl-2. We conclude that chronic UUO inhibits bcl-2 expression in selected tubules of the obstructed kidney which contributes to activation of apoptosis and progressive renal damage in either neonatal or adult kidneys. Dysregulation of apoptosis may be a response to renal injury similar to that underlying the development of cystic kidney disease or renal dysplasia.

译文

单侧输尿管梗阻 (UUO) 导致成人和新生儿阻塞肾脏中广泛的肾小管凋亡。癌蛋白bcl-2抑制许多形式的凋亡,而相关蛋白bax促进凋亡。为了评估bcl-2,bax和细胞凋亡在肾脏对UUO的反应中的相互作用,对成年和新生大鼠进行UUO或假手术,并在14天后收获肾脏。通过Tunel技术鉴定凋亡细胞,并通过免疫化学确定bcl-2和bax的分布。在成年人和新生儿中,阻塞的肾脏中存在肾小管和间质凋亡,但在完整的肾脏中不存在。在成人和新生儿中,假手术和完整肾脏均存在弥漫性肾小管bcl-2和bax染色。虽然阻塞的肾脏中分散的非凋亡小管的bcl-2增加,但扩张的凋亡小管的染色却很少。这些结果与bcl-2正常抑制肾小管凋亡的前提相符。bax染色在阻塞的肾脏小管中的分布与bcl-2的分布重叠。我们得出的结论是,慢性UUO抑制了阻塞肾脏选定肾小管中的bcl-2表达,这有助于激活新生或成年肾脏的凋亡和进行性肾损伤。细胞凋亡失调可能是对肾损伤的反应,类似于囊性肾脏疾病或肾发育不良的潜在反应。

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