摘要
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 study the effect of hypoxia-inducible factor-1α （HIF-1α） on endotheliumdependent and -independent vascular relaxation reactivity following hemorrhagic shock in rats. Methods Two hundred and eight SD rats were randomly divided into normal control group, shock control group and oligomyein group. Shock control and oligomycin groups were further divided into 0, 0.5, 1, 2, 3, and 4 h groups after hemorrhagic shock. Superior mesenteric artery （SMA） was used to compare the changes in vascular response to sodium nitroprusside （SNP） and acetylcholine （Ach） with or without administration of oligomycin, a kind of specific HIF-1α blocking agent, and to determine the expression of HIF-1α mRNA by RT-PCR. Results The vascular reactivity of SMA to SNP in each shock group was significantly decreased at lower concentrations （ 10^ -9, 10^ -8 and 10 ^-7mol/L） of SNP and oligomycin further depressed the response of SMA to SNP. The response of SMA to Ach in shock groups was transiently decreased after shock, and then began to increase during the compensatory period of shock, reached its peak at 2 h after shock, and then decreased again. The response of SMA to Ach decreased significantly in early hemorrhagic shock （0 to 1 h, P 〈0.01 ） and increased in late hemorrhagic shock （2 to 4 h） after administration of oligomycin. HIF-1α mRNA expression increased in a timedependent manner and reached its peak at 4 h following shock, which was positively correlated with endothelium-dependent vascular relaxation reactivity in early hemorrhagic shock（ r = 0. 984, P 〈 0.05 ）, negatively correlated with late hemorrhagic shock and did not correlate with endothelium-dependent vascular relaxation reactivity （r = - 0. 999, P 〈 0.05 ）. Conclusion Endothelium-dependent vascular relaxation reactivity increases in early hemorrhagic shock and decreases in late hemorrhagic shock. Endothelium-independent vascular relaxation reactivity decreases markedly following hemorrhagic shock. HIF-1α plays an important role in regulation of endothelium-dependent and independent vascular relaxation reactivity following hemorrhagic shock.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2010年第4期319-323,共5页
Journal of Third Military Medical University
基金
国家重点基础研究发展计划(973计划,2005CB522601)
国家自然科学基金重点项目(30830053)~~
关键词
失血性休克
血管
缺氧诱导因子-1Α
舒张反应
hemorrhagic shock
blood vessel
hypoxia-inducible factor-1α
relaxation reactivity
