Rosenberg M E, Paller M S
Department of Medicine, University of Minnesota, Minneapolis.
Kidney Int. 1991 Jun;39(6):1156-61. doi: 10.1038/ki.1991.146.
Recovery from renal ischemia requires regeneration of damaged tubular epithelium. Previous studies have examined the expression of proto-oncogenes and growth factors after ischemia, but the response of genes coding for structural and functional genes has not been scrutinized. Rats were subjected to 40 minutes of renal artery occlusion and 60 minutes to 96 hours of reperfusion. Total RNA was isolated and mRNA for the structural protein actin, the enzymes superoxide dismutase and renin, the proto-oncogene c-fos, the nuclear protein histone H2b, and the putative marker for cell injury TRPM-2 was quantitated by Northern hybridization. Expression of the proto-oncogene c-fos was seen early but for only short duration. Histone gene expression was not markedly increased until 24 hours after ischemia, but remained increased for several days. Renin mRNA was undetectable one hour after ischemia, but was present in normal amounts at 24 and 48 hours. In contrast, superoxide dismutase mRNA was present in decreased amounts 24, 48, and 96 hours after ischemia. TRPM-2 gene expression was greatly increased 24 to 72 hours after ischemia and began decreasing at 96 hours. This selective sequence of gene expression or repression after renal ischemia might maximize the proliferative repair process. This information will be useful for designing therapies to further enhance recovery from acute renal injury.
肾缺血的恢复需要受损肾小管上皮的再生。以往的研究检测了缺血后原癌基因和生长因子的表达，但编码结构和功能基因的基因反应尚未得到详细研究。对大鼠进行40分钟的肾动脉阻断，并进行60分钟至96小时的再灌注。分离总RNA，通过Northern杂交定量分析结构蛋白肌动蛋白、超氧化物歧化酶和肾素、原癌基因c-fos、核蛋白组蛋白H2b以及细胞损伤推定标志物TRPM-2的mRNA。原癌基因c-fos的表达出现较早，但持续时间较短。组蛋白基因表达直到缺血后24小时才明显增加，但持续增加数天。肾素mRNA在缺血后1小时检测不到，但在24小时和48小时时含量正常。相比之下，超氧化物歧化酶mRNA在缺血后24、48和96小时含量减少。TRPM-2基因表达在缺血后24至72小时大幅增加，并在96小时开始下降。肾缺血后这种基因表达或抑制的选择性序列可能会使增殖修复过程最大化。这些信息将有助于设计进一步促进急性肾损伤恢复的治疗方法。
