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目的探讨缺氧诱导因子-1α(Hypoxia-inducible factor-1,HIF-1α)对失血性休克大鼠内皮依赖性和内皮非依赖性血管舒张反应性的影响。方法208只SD大鼠随机分为正常对照组、休克组和寡霉素(Oligomycin,HIF-1α特异性拮抗剂)处理组,休克组和寡霉素处理组又分为休克即刻、0.5、1、2、3、4h6个时相点;取肠系膜上动脉(superior mesenteric artery,SMA)制成血管环,分别观察休克后和注射寡霉素后对硝普钠(sodium nitroprusside,SNP,内皮非依赖性舒张剂)和乙酰胆碱(acetylcholine,Ach,内皮依赖性舒张剂)诱导的舒张反应性变化。RT-PCR法分析HIF-1αmRNA的表达变化规律。结果各休克组SMA血管环对低浓度SNP(10-9、10-8、10-7mol/L)的舒张反应性降低;寡霉素可进一步降低其最大舒张反应。休克后血管对Ach的舒张反应性呈下降-上升-再下降的趋势,即在休克即刻有一短暂降低,随后呈代偿性增加,休克2h达峰值,2h后呈下降趋势;使用寡霉素后,血管对Ach的舒张反应性在休克早期(休克即刻～休克1h)显著下降(P<0.01),而在休克晚期(休克2～4h)呈上升趋势。与正常组相比,休克后HIF-1αmRNA的表达增加;与休克早期内皮依赖的舒张反应呈正相关(r=0.984,P<0.05),而与休克晚期的呈负相关(r=-0.999,P<0.05),与内皮非依赖的舒张反应性没有相关性。结论内皮依赖性血管舒张反应在休克早期存在代偿性回升,晚期失代偿降低;内皮非依赖性血管舒张反应在休克后呈持续降低。HIF-1α在休克后内皮非依赖性和内皮依赖性舒张反应性的调节中均具有重要作用。
Objective To investigate the effect of hypoxia inducible factor-1 (HIF-1α) on endothelium-dependent and endothelium-independent vasodilation in hemorrhagic shock rats. Methods 208 SD rats were randomly divided into normal control group, shock group and oligomycin (HIF-1α specific antagonist) treatment group, shock group and oligomycin treatment group was divided into shock immediately, 0.5,1 , 2, 3, 4h 6 time points. Vascular rings were made from the superior mesenteric artery (SMA). After shock and injection of oligomycin, sodium nitroprusside (SNP) And diastolic activity induced by acetylcholine (Ach, endothelium-dependent relaxation agent). RT-PCR analysis of HIF-1αmRNA expression changes. Results The vasorelaxation activity of SMA vascular rings in each shock group was lower than that of low concentration SNPs (10-9,10-8,10-7 mol / L). Oligomycin could further reduce the maximal relaxation response. After shock, the diastolic reactivity of blood vessels to Ach decreased-increased-then decreased, that is, there was a transient decrease immediately after shock and then compensatory increase. The peak value reached the peak at 2h and then decreased after 2h. After using oligomycin , The vasorelaxation of Ach decreased significantly in early shock (shock ~ shock 1h) (P <0.01), but increased in late shock (2-4 h). Compared with the normal group, the expression of HIF-1αmRNA increased after shock; it was positively correlated with the endothelium-dependent relaxation in early stage of shock (r = 0.984, P <0.05), but negatively correlated with the late stage of shock (r = -0.999, P <0.05), but not with endothelium-independent diastolic reactivity. Conclusion Endothelium-dependent vasorelaxation may have compensatory recovery in the early stage of shock and decrease of late decompensation. Endothelium-independent vasodilation may continue to decline after shock. HIF-1α plays an important role in the regulation of endothelium-independent and endothelium-dependent relaxation responses after shock.