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1、PPAR-γ在高血压血管平滑肌细胞表型转化中的作用研究*张莉莉1,李敬诚2,王景周2,谢鹏1(1重庆医科大学附属第一医院神经内科,重庆,400016;2第三军医大学大坪医院野战外科研究所神经内科,重庆,400042)摘要:目的:观察过氧化物酶体增殖物激活受体-γ(peroxisomeproliferatoractivatedreceptors–γ,PPAR–γ)在高血压血管平滑肌细胞(VSMC)表型转化中的作用。方法:应用基因重组技术使PPAR–γ过表达和表达抑制,Westernblot方法检测分化型VSMC标志物α-SMA和未分化型
2、VSMC标志物OPN的蛋白表达,应用DNA合成率检测和细胞计数的方法测定细胞增殖率,常规病理切片和HE染色观察血管形态学改变。结果:①PPAR–γ激动剂罗格列酮可降低SHR大鼠血压,并改善主动脉血管重构;②SHR大鼠主动脉中OPN表达增多而α-SMA表达减少,应用罗格列酮可抑制上述改变;③SHR大鼠来源的VSMC中OPN表达增多而α-SMA表达减少,细胞增殖率升高,PPAR–γ过表达使细胞增殖率降低,并抑制OPN和α-SMA的表达改变。结论:PPAR–γ可抑制高血压VSMC向未分化表型的转化,可能是其改善高血压血管重构的重要机制。关键
3、词:过氧化物酶体增殖物激活受体-γ(PPAR–γ),血管平滑肌细胞(VSMC),血管重构,表型转化中图法分类号:文献标识码:AEffectofperoxisomeproliferators-activatedreceptor-gammaonphenotypictransformingofvascularsmoothmusclecellinhypertensionZHANGLi-li1,LIJing-cheng2,WANGJing-zhou2,XIEPeng1(1DepartmentofNeurology,FirstAffiliated
4、Hospital,ChongqingUniversityofMedicalSciences,Chongqing,400016;2DepartmentofNeurology,InstituteOfSurgeryResearch,DapingHospital,TheThirdMilitaryMedicalUniversity,Chongqing400042)[Abstract]ObjectiveToobservetheeffectofperoxisomeproliferatorsactivatedreceptorgamma(PPAR-γ)
5、onphenotypictransformingofvascularsmoothmusclecell(VSMC)inhypertension.MethodsGeneticrecombinationtechnologywasusedtoover-expressorsilencetheexpressofPPAR-γ.ExpressionofOPNandα-SMA,whichrepresenttheundifferentiatedanddifferentiatedVSMCrespectively,weredetectedbywesternb
6、lot.CellproliferationwasdeterminedbydetectionofDNAsynthesisandcellcounting.Thechangesofarteriesweredetectedbypathologicalstudy.Results①RosiglitazonedecreasedbloodpressureandamelioratedthevascularremodelingofaortainSHR.②AortaofSHRshowedanup-regulationofOPNanddown-regulat
7、ionofα-SMA,whichwereinhibitedbyrosiglitazone.③VSMCcamefromSHRshowedanup-regulationofOPNanddown-regulationofα-SMAandincreasedcellproliferation,andthesechangeswereallinhibitedbyrosiglitazone.ConclusionsPPAR-γcouldinhibitthephenotypictransformingofVSMC,andthismightberespon
8、sibleforitsameliorationofvascularremodelinginhypertension.【Keywords】peroxisomeproliferatorsactivatedreceptorga