创伤性急性肾衰时肾脏分离肾小管上皮细胞DNA损伤的意义

目的探讨肾小管上皮细胞DNA损伤在急性肾功能衰竭（acute renal failure，ARF）中的意义。方法Wistar大鼠108只，等分为大、小剂量及对照组，分别于后肢肌肉注射10、5ml／kg50％甘油及10ml／kg生理盐水。于1、3、6、12、24、48h测定血尿素氮（blood urea nitrogen，BUN）、肌酐（creatinine，Cr），取肾脏分离肾小管上皮细胞，单细胞凝胶电泳（single cell gel electrophoresis，SCGE）技术测定DNA损伤。结果两实验组BUN、Cr分别于12、6h起较对照组显著升高（P＜0．05，P＜0．01），两实验组间BUN和Cr分别在12h和24h起出现显著差异（P＜0．05，P＜0．01），表明肾功能受损程度不同。肾脏分离肾小管上皮细胞DNA损伤对甘油注射呈现剂量和时间依赖性，其变化趋势与尿脱落细胞DNA损伤相似，但损伤程度较轻。结论DNA损伤、细胞脱落及凋亡等变化参与了肾小管上皮细胞的损伤，是ARF病理生理变化过程“多米诺骨牌”中的重要环节，在预防或及时阻断其发生在ARF的救治中有重要意义。

DNA damage of renal tubular epithelial cells in acute renal failure

Objective To investigate the role of DNA damage in the development of acute renal failure(ARF),especially at the early stage.Methods ARF of different degree was induced by intramuscular injection of 10,5 ml/kg glycerol or physiological saline to 108 Wistar rats(n=36 for each treatment).Cr and BUN in serum were detected at 1,3,6,12,24 and 48 h after injection.At the same time,DNA damage of tubular cells isolated from kidney and exfoliative tubular cells in urine were assayed by single cell gel electrophoresis assay(SCGE).Results After glycerol injection,BUN and Cr increased significantly with statistical difference among groups.The DNA damage in the tubular cells of two glycerol treated groups presented earlier than Cr and BUN in serum.The DNA damage of tubular cells showed a dose and time-dependent manner with glycerol dose and positive relationship to the degree of renal function damage.But the DNA damage was more serious in urinary exfoliative tubular cells.Conclusion The results suggest that cell exfoliation and DNA damage are important mechanisms of tubular cell injury in ARF,and their prevention and blocking may play an important role in the treatment of ARF.