HIF和VEGF在低氧性肺动脉高压中的调控作用.doc

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1、HIF和VEGF在低氧性肺动脉高压中的调控作用【摘要】目的:观察低氧诱导因子-1α（HIF-1α）蛋白和血管内皮生长因子（VEGF）蛋白在低氧性肺动脉高压小鼠肺内的表达，探讨HIF和VEGF在其中的调控作用。方法:建立低氧性肺动脉高压小鼠模型，SPF级雄性C57BL/6小鼠16只，随机分为正常对照组（C组），低氧、高二氧化碳4w组（H组），每组8只。测二组小鼠的右心室收缩压(RVSP)和右心室重量比RV/（LV+S）。光镜下观察右心室和肺组织病理学改变。应用免疫组化技术检测肺细小动脉上HIF-1α蛋白和VE

2、GF蛋白的表达。结果:H组小鼠RVSP明显高于C组，且RV/（LV+S）亦有增加。光镜下肺细小动脉管腔变窄管壁增厚，中膜平滑肌细胞肥大增生。免疫组织化学显示:H组小鼠肺细小动脉HIF-1α蛋白和VEGF蛋白免疫组化吸光度高于对照组；VEGF蛋白与HIF-1α蛋白表达呈正相关。结论:慢性低氧使HIF-1α蛋白和VEGF蛋白在肺细小动脉表达增加，二者参与小鼠肺动脉高压的形成和发展过程。【关键词】低氧诱导因子-1α血管内皮生长因子肺动脉高压慢性低氧高二氧化碳小鼠Abstract:Objective:Toexplo

3、retheexpressionofHypoxia-induciblefactor1α（HIF-1α）proteinandvascularendothelialgrowthfactor(VEGF)proteininmicewithpulmonaryhypertensioninducedbychronichypoxichypercapnia,andinvestigatewhetherHIFsignalpathtoregulatetheexpressionofVEGF.Methods:SixteenmaleC57

4、bl/6micewererandomlydividedintotwogroups:thecontrolgroup(groupC)andthegroupwithhypoxichypercapniafor4weeks(groupH).Therightventricularsystolicpressure(RVSP)andtheratioofRV/(LV+S))weremeasured.Lungsectionswerestainedwithhematoxylinandeosin(H&E)formorpho

5、logicstudiesunderlightmicroscope.TheexpressionofHIF-1αproteinandVEGFproteinofpulmonaryarterioleswasalsoobservedwithimmunohistochemistry.Results:①ThevaluesoftheRVSP,RV/LV+SingroupHweresignificantlyhigherthanthatingroupC.②Thevesselwallsofthepulmonaryarteriol

6、esofgroupHwerethicken,thesmoothmusclecellsintunicamediawereproliferatedandthelumensofthepulmonaryarterioleswerenarrowedunderlightmicroscope.③BothHIF-1αproteinandVEGFproteinstainingwerepositiveinthelungofpulmonaryarteriolesofgroupHwithimmunohistochemistry.T

7、heaverageopticaldensityofHIF-1αandVEGFproteinwithimmunohistochemistryinthepulmonaryarteriolesingroupHwassignificantlyhigherthanthatingroupC.TherewaspositivecorrelationbetweenVEGFproteinandHIF-1αprotein.Conclusion:HIF-1αproteinandVEGFproteinareinducedtoexpr

8、essbychronichypoxic,andinvolvedinthepathogenesiswithpulmonaryhypertensioninmice.4Keywords:HIF-1α;VEGF;pulmonary;hypoxia;hyperoapnia;mice慢性阻塞性肺疾病(chronicobstructivepulmonarydiseaseCOPD)是一种具有气流受限特征的疾病，随着病情的进展，长