肺栓塞大鼠肺动脉和右心室HIF-1α的表达

Expressions of Hypoxia-inducible factor-1α in Pulmonary Artery and Right Ventricular in Rats with Pulmonary Thromboembolism

目的观察肺栓塞大鼠肺细小动脉和右心室HIF-1浕的表达,并探讨其在疾病发展过程中的作用。方法大鼠,体外制备栓子,经颈静脉注入栓子,两周后同法进行二次栓塞。测定平均肺动脉压(mPAP);心肺组织:(1)测定肺动脉相对中膜厚度(PAMT)和管壁面积/管总面积(WA/TA)及右心室肥大指数(RVHI);(2)分别用原位杂交方法和免疫组化方法检测肺动脉和右心室HIF-1αmRAN和HIF-1α蛋白的表达。结果(1)mPAP从4周组开始持续明显升高(P均<0.01);PAMT和WA/TA在栓塞8周组开始升高(P均<0.05);RVHI在12周组明显高于对照组(P<0.01)。(2)肺动脉和右心室HIF-1αmRAN2周组开始升高(P均<0.01);肺动脉HIF-1α蛋白3天组开始升高(P均<0.01),右心室HIF-1α蛋白1周开始升高(P均<0.01)。(3)相关关系:肺动脉HIF-1αmRAN和HIF-1α蛋白均与mPAP、PAMT和WA/TA呈正相关关系;右心室HIF-1αmRAN和HIF-1α蛋白均与mPAP和RVHI呈正相关关系。结论HIF-1α在肺动脉和右心室表达明显增高并与肺动脉高压,肺动脉重构的病理生理过程有明显相关关系。

Objective To investigate the expressions of Hypoxia-inducible factor-1α（HIF-1α） of small pulmonary artery and fight ventricular in rats with pulmonary thromboembolism and discuss the effect of HIF-1α during the process of FIE. Methods The rats were injected thrombi into jugular vein two times in two weeks, and then were measured the mean pulmonary artery pressure （mPAP）. The experiment method was followed： （1） measuring the relative medial thickness of small pulmonary arteries （PAMT） and vessel wall area/total area （WA/TA） and evaluating the right ventricular hypertrophy index （RVHI）. （2） Figuring out the expression of HIF-1α pro- tein in small pulmonary arteries and in right ventricular by immunohischemistry and the expression of HIF-1α mRNA by situ hybridization method. Result In the model groups, （1）mPAP of 4-12 week groups were higher than that of the control groups（P〈0.01, respectively） ; PAMT and WA/TA began to increase from 8 week groups （P〈0.05） ; the RVHI of 12week groups were higher than that of the control groups （P〈0.01）. （2） The expression of HIF-1α mRNA of pulmonary arteries and right ventricle began to increase from 2 week groups （P〈0.01）; The expression of HIF-1α protein of pulmonary arteries began to increase remarkably from 3-day-groups; The expression of HIF-1α protein began to increase from 1 week groups （P〈0.01, respectively）. （3） There are positive correlations between expressions of HIF-1α protein, HIF-1α mRNA in pulmonary artery and mPAP, PAMT, and WA/TA; there are positive correlations between expressions of HIF-1α protein, HIF-1α mRNA in right ventricle and mPAP, RVHI. Conclusion The expressions of HIF-1α protein and HIF-1α mRNA of pulmonary arteries and right ventricle in model groups were higher than those of control groups. These dynamic changes of HIF-1α protein and HIF-1α mRNA may have important contribution to the development of pulmonary hypertension and vascular remode-ling after pulmonary tlnromboembolism in rats.