低血容量性休克大鼠缺氧诱导因子1α的表达及其在血管低反应性发生中的作用  

The changes in the HIF-1αexpression during hypovolemic shock and its role in the pathogenesis of vascular hyporeactivity

作　　者：张瑗[1] 刘良明[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所第二研究室,创伤,烧伤与复合伤国家重点实验室,重庆400042

出　　处：《中华烧伤杂志》2006年第5期343-346,共4页Chinese Journal of Burns

基　　金：国家重点基础研究发展计划资助项目(2005CB522601)

摘　　要：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CObjective To investigate the changes in the expression of HIF-lct in rat superior mesenteric artory（ SMA ） tissue after hypovolemic shock （HS） , and its relationship with the pathogenesis of vascular hyporeactivity. Methods One hundred and twelve SD rats were used in the study, and they were randomly divided into HS group（ n = 56）and treatment group （n = 56, with intraperitoneal injection of 9 μg/kg oligomycin 4 h before the experiment）. Arterial blood of the rats in each group were harvested at 0.0, 0.5, 1.0,2.0,3.0,4.0,6.0 post-injury hour（ P1H ） , respectively, with 8 rats at each time-points. Then the rats were sacrificed and superior mensenterie arteries （SMA） were harvested. Other 8 rats without any treatment served as normal controls. The changes in mRNA expression of HIF-1α,inducible nitric oxide synthase（iNOS） and hameoxygenase 1 （ HO-1 ） were determined with RT-PCR. The contraction of vascular ring of SMA to gradient concentration of norepinephrine （NE） was measured with ex vitro vascular ring tension determination method. The plasma content of carbon monoxide and nitric oxide were measured with sodium dithionite reduction method and nitrate reductase method, respectively. Results Compared with normal controls,Vascular reactivity of SMA in HS group increased compensatorily during early stage of HS（0.0 - 1.0 h） , and peaked at 0.5h. The pD2 （ - log[ NE 1 ） of NE decreased , but the maximal contraction （Emax） was above the normal level during 0.0 - 1.0 PIH（ P 〈0.01 ）. During the middle and late shock stage, the vascular reactivity decreased gradually. The Emax decreased, pD2 increased, and the Emax was below the normal level at 4.0 PIH （ P 〈 0.01 ）. The increase of vascular reactivity in treatment group was partially inhibited during early stage after injury（ P 〈 0.01 ）. The Emax was （2.01 ± 0.22） g/mg at 0.5PIH,which was obviously lower than that in HS group[（2.96±0.18）g/mg , P 〈0.05]. In decompensated period of HS, the vascu

关 键 词：休克 缺氧诱导因子1Α 血管反应性 

分 类 号：R459.7[医药卫生—急诊医学]