祖细胞样肾小管细胞在急性肾小管坏死修复中的作用

目的 观察大鼠缺血性急性肾小管坏死（ATN）后肾脏内溴脱氧尿嘧啶核苷（BrdU）及Pax2阳性细胞的动态变化，探讨祖细胞样肾小管细胞在ATN修复过程中的作用。 方法 钳夹SD大鼠左侧肾动脉60 min后再开放血流，建立缺血性ATN模型。给予细胞分裂增殖标记物BrdU负荷，分别于术后第1、3、5、7、14、21、28天收获肾脏标本，进行BrdU和肾源性标记物Pax2免疫组织化学染色，以及BrdU和Pax2、间充质细胞标记物波形蛋白（vimentin）、细胞凋亡标记物活化caspase-3的双重染色，观察BrdU阳性细胞的数量和分布变化。 结果 ATN组术后左肾出现明显的近端肾小管上皮细胞广泛性坏死，BrdU阳性细胞明显增加，第3天达到高峰，显著高于假手术对照组和右肾（P < 0.01）。而右肾BrdU阳性细胞亦显著高于假手术对照组（P < 0.01）。双重染色显示BrdU阳性细胞同时表达Pax2和波形蛋白，但未见同时表达活化的caspase-3。 结论 大鼠在经历缺血性ATN后，肾脏内祖细胞样小管细胞被动员。其修复可能是通过逆分化、增殖和再分化过程来完成的。而细胞因子可能在这过程中起着调控作用。

Role of renal progenitor-like tubular cells in the repair of acute renal tubular necrosis

Objective To elucidate the role of renal progenitor-like tubular cells in the repair process after acute tubular necrosis (ATN) induced by ischemia. Methods Rat ATN was developed by clamping left kidney artery for 60 minutes, and bromodeoxyuridine(BrdU), a cell division and proliferation marker, was administrated one hour before rats were sacrificed. Kidneys were isolated at 1, 3, 5, 7, 14, 21, 28 days after injury. The proliferative and apoptotic cells were determined by immunostaining using anti-BrdU, Pax2 (an embryonic renal marker), vimentin (an immature mesenchymal cell marker), and activated caspase-3 (a cell apoptosis marker). Results Cell death was found in tubules at day 1 after ischemia and reperfusion injury. BrdU-positive cells were dramatically increased and reached peak at day 3 after injury. In addition, the number of BrdU positive cells in the contralateral kidney was significantly increased compared to sham operated group. Double immunostaining showed that BrdU-positive cells co-expressed Pax2 or vimentin, but not activated caspase-3. Conclusions Renal progenitor-like tubular cells may play a predominant role in repair process following ATN in rats. They may dedifferentiate, proliferate, and then redifferentiate into mature tubular cells. Growth factors may regulate the repair process.