摘要目的 研究肾缺血再灌注损伤(IRI)时肾组织低氧诱导因子-1α(HIF-1α)mRNA表达的变化,探讨高压氧(HBO)对肾IRI的作用及其机制.方法 42只Wistar大鼠分为对照组、肾IRI组和HBO治疗组,对照组6只,其余2组各18只,建立大鼠肾IRI模型.肾IRI组和HBO治疗组分别于再灌注后1,3,5 h(每个时间点6只)采血测定肾功能,荧光定量聚合酶链反应(PCR)检测肾组织HIF-1α mRNA的表达,同时用电镜观察组织超微结构的变化.结果 ①随着再灌注时间的延长,血清Cr的水平逐渐增高,显著高于对照组(P<0.05);HBO治疗后血清Cr水平显著降低(P<0.05).②肾IRI组在再灌注1 h时肾组织HIF-1amRNA表达量明显低于正常水平,3 h时明显高于对照组(P<0.05),5 h时基本恢复至正常水平(P>0.05);与肾IRI组相比,HBO治疗组再灌注后1 h和3 h时HIF-1α mRNA表达量明显增加(P<0.05),5 h时显著减少(P<0.05).③随着时间的延长,肾IRI组肾小管上皮细胞内质网扩张、线粒体肿胀等损伤逐渐加重;HBO治疗后肾损伤的程度明显减轻,线粒体基本恢复正常,再灌注1 h和3 h时肾损伤减轻的程度明显优于再灌注5 h时.结论 HIF-1αmRNA参与了肾IRI的病理生理过程.HBO通过提前启动和上调HIF-1α mRNA的表达,明显减轻了肾IRI,保护了肾功能.HBO早期干预更有利于肾IRI的治疗.

abstractsObjective To study the expression of hypoxia inducible factor-1alpha (HIF-1α) mRNA in re-nal tissue after renal ischemia-reperfusion injury (IRI), and to investigate the effect of hyperbaric oxygen (HBO) on renal IRI and its mechanism. Methods Forty-two Wistar rats were randomly divided into a normal control group(n =6), a renal IRI group (n=18) and an HBO treatment group (n=18). Renal IRI models were established in all the rats. The plasma levels of Cr in the experimental groups were then measured after 1, 3 and 5 hours. The expres-sion of HIF-1α mRNA was also detected using real-time PCR and immunohistochemistry. Kidney tissue sections were preserved for ultrastructure examination. Results (1) The average levels of plasma Cr in the renal IRI group were significantly higher than those in the control group. Compared with the renal IRI group, plasma Cr was significantly lower in the HBO treatment group. (2) The average expression of HIF-1α mRNA was significantly lower an hour after reperfusion, but significantly higher after 3 hours than in the control group. There was no significant difference by the 5th hour after reperfusion. In the HBO treatment group, HIF-1α mRNA was up-regulated significantly at the 1st and 3rd hour after reperfusion compared with the renal IRI group, but it was reduced significantly by the 5th hour after reperfusion. (3) The severity of the kidney injury increased gradually with time in the renal IRI group. After HBO treatment, however, the damage to the renal tissues decreased significantly. Conclusions HIF-1α mRNA plays an important role in the development of renal IRI. The damage to renal tissues and renal function improves significantly after reperfusion and HBO treatment through earlier priming and up-regulating of HIF-1α mRNA expression. HBO should be applied early to help prevent renal IRI.