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目的观察低血容量性休克大鼠肠系膜上动脉(SMA)血管组织中缺氧诱导因子1α(HIF-1α)的表达情况及其与血管低反应性发生的关系。方法将112只SD大鼠建立低血容量性休克模型后分为休克组(56只)、给药组(56只,于建立休克模型前4 h在大鼠腹腔内注射9μg／kg寡霉素)。于伤后0.0(10-15 min)、0.5、1．0、2．0、3．0、4．0、6．0 h,采大鼠动脉血后处死大鼠取SMA,每组每时相点8只。采用离体血管环张力测定技术测定血管环对梯度浓度去甲肾上腺素(NE)的收缩力;逆转录-聚合酶链反应(RT-PCR)半定量分析法检测SMA血管组织中HIF-1α、诱导型一氧化氮合酶(iNOS)、血红素氧合酶1(HO-1)mRNA的表达水平;连二亚硫酸钠还原法和硝酸还原酶法分别测定其全血一氧化碳(CO)浓度和血浆一氧化氮(NO)含量。另取8只大鼠作为正常对照组,不作处理,留取标本检测以上指标。结果与正常对照组比较,休克组大鼠伤后早期(0．0-1．0 h)血管反应性增高,伤后0．5 h达峰值,血管环对NE的最大收缩反应(Emax)增大,NE的50％最大效应的负对数克分子浓度(pD2)减小;伤后0．5-1．0 h Emax值均高于正常对照组(P<0．01);休克中、后期,血管反应性进行性下降,Emax减小、pD,增大,伤后4．0 h Emax低于正常对照组(P<0．01)。给药组伤后早期(0．0-1．0 h)血管反应性增高部分受抑制(P<0．05),伤后0．5 h Emax值为(2．01±0．22) g／mg,明显低于休克组[(2．96±0．18)g／mg,P<0．05]。休克晚期给药组血管反应性轻度回升,与休克组伤后4．0、6．0 h比较,差异有统计学意义(P<0．05或0．01)。与正常对照组比较,休克组伤后HIF-1αmRNA的表达呈稳步增高,伤后4．0 h达峰值(P<0．01);iNOS、HO-1mRNA表达水平亦逐渐增高,分别于伤后2．0、4．0 h达峰值(P<0．01)。与正常对照组比较,休克组随着病情的发展全血CO浓度和血浆NO含量呈逐渐升高的趋势。与休克组相比,给药组全血CO浓度基本稳定在正常范围内,血浆NO含量也明显降低。结论低血容量性休克可引起血管反应性的双相变化。HIF-1α在血管低反应性的形成中发挥了重要作用。
Objective To investigate the expression of hypoxia inducible factor 1α (HIF-1α) in vascular tissue of superior mesenteric artery (SMA) in hypovolemic shock rats and its relationship with vascular hyporeactivity. Methods One hundred and twelve SD rats were divided into shock group (56 rats) and hypovolemic shock rats (56 rats). Rats were injected intraperitoneally with 9μg / kg oligomycin ). After injury, rats were sacrificed for 0.0 (10-15 min), 0.5, 1.0, 2.0, 3.0, 4.0 and 6.0 h after the arterial blood was drawn, and rats were sacrificed every hour Point 8. The contractile force of vascular ring on the concentration of norepinephrine (NE) was measured by using the exsangial vascular ring tensiometry. The expression of HIF-1α, (INOS) and heme oxygenase-1 (HO-1) mRNA were detected by enzyme linked immunosorbent assay (ELISA). The levels of CO and plasma CO in whole blood were determined by sodium dithionite reduction and nitrate reductase Nitric oxide (NO) content. Another 8 rats as a normal control group, without treatment, specimens were taken to detect the above indicators. Results Compared with the normal control group, the rats in the shock group had higher vascular reactivity (0.0-1.0 h) and a peak value at 0.5 h after injury, and the maximum systolic response (Emax) of the vascular ring to NE increased The negative logarithm molar concentration (pD2) of 50% of the maximal effect of NE and NE decreased, while the Emax of 0.5-1.0 h after injury was higher than that of the normal control group (P <0.01) In the later period, the vascular reactivity decreased progressively, the Emax decreased, the pD increased, and the Emax 4.0 h after injury was lower than that of the normal control group (P <0.01). The vasoreactivity in the early stage of injury (0.0-1.0 h) in the treated group was partially inhibited (P <0.05), and the Emax at 0.5 h after the injury was (2.01 ± 0.22) g / Mg, significantly lower than that in shock group [(2.96 ± 0.18) g / mg, P <0.05]. Vascular reactivity was slightly increased in the late shock group compared with 4.0 and 6.0 h after shock in the shock group (P <0.05 or 0.01). Compared with the normal control group, the expression of HIF-1αmRNA in shock group increased steadily and peaked at 4.0 h (P <0.01), and the expression of iNOS and HO-1mRNA also increased gradually 2.0, 4.0 h peak (P <0.01). Compared with the normal control group, the whole blood CO concentration and plasma NO content increased gradually with the progression of the disease in shock group. Compared with the shock group, the CO concentration in the whole blood of the administration group was basically stable within the normal range, and the content of NO in the plasma was also significantly reduced. Conclusions Hypovolemic shock can induce biphasic changes of vascular reactivity. HIF-1α plays an important role in the formation of vascular hyporeactivity.