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1、丹桔胶囊对血管紧张素Ⅱ损伤血管内皮功能的保护作用研究易佳丽1,张钟爱2,骆天炯2,刘保林1[收稿日期]2010-01-25[基金项目]南京市科技发展计划赞助项目(200805013)[通讯作者]刘保林,教授;Tel(025)86185146;E-mail:njlbl55@sohu.com[作者简介]**易佳丽,在读硕士,研究方向:生化药理学;E-mail:yijiali112@163.com(1中国药科大学中药药理学教研室,江苏南京211198;2南京市中医院老年病科,江苏南京210001)[摘要]目的:观察丹桔胶囊对血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)
2、损伤血管内皮功能的保护作用。方法:制备大鼠胸主动脉环,观察丹桔胶囊提取剂对抗AngⅡ引起的胸主动脉环收缩反应;AngⅡ刺激人脐静脉血管内皮细胞(humanumbilicalveinendothelialcells,HUVEC)以反转录—聚合酶链反应(RT-PCR)方法检测HUVEC的内皮素(ET-1)mRNA表达水平;蛋白质印迹(Westernblot)方法检测HUVEC中细胞外信号调节激酶(extracellularsignal-regulatedkinase,ERK)和核转录因子κB(nuclearfactorκB,NF-κB)的活化情况。结果:AngⅡ引起胸主动
3、脉收缩,丹桔胶囊制剂能显著对抗血管收缩作用,下调AngⅡ刺激所致的HUVEC细胞ET-1mRNA过度表达,抑制ERK1/2磷酸化,同时对NF-的活化表现出显著的抑制作用。p65位移、IκB-α磷酸化降解,丹桔胶囊上述抑制作用均呈现浓度依赖性。结论:丹桔胶囊抑制AngⅡ对血管内皮功能的损伤,其机制与降低ET-1表达,抑制ERK/NF-κB途径活化有关。[关键词]丹桔胶囊;血管紧张素Ⅱ;主动脉;人脐静脉血管内皮细胞;内皮素ProtectiveEffectsandMechanismofJuDanCapsuleonangiotensinⅡ-InducedEndothelial
4、DysfunctionsYIJia-li,ZHANGZhong-ai,LUOTian-jiong,LIUBao-lin(1DepartmentofPharmacologyofChineseMateriaMedica,ChinaPharmaceuticalUniversity,Nanjing211198,China;2DepartmentofGerontology,HospitalofTraditionalChineseMedicineofNanjing,Nanjing210001,China)[Abstract]Objective:Toobservethethepro
5、tectiveeffectofJuDancapsuleonvascularendothelialdysfunctionsinducedbyangiotensinⅡ(AngⅡ).Methods:TheAngⅡ-inducedcontractionofrataorticringsweretestedintissuebath;Theexpressionofendothelin(ET)-1mRNAwasevaluatedbyRT-PCR;RT-PCRwasusedtoevaluateendothelin(ET)-1mRNAexpressioninHumanumbilicalv
6、einendothelialcells(HUVEC);Theactivationofextracellularsignal-regulatedkinase(ERK)andnucleartranscriptionfactor(NF-κB)anditsinhibitor(IκB-α)weredetectedbyWesternblotinHUVEC.Results:Theresultsshowedthat1×10-7mol·L-1AngⅡincreasedcontractionofrataorticrings,ET-1mRNAexpression,ERK1/2phospho
7、rylation,NF-κBp65displacementandIκB-αphosphorylationdegradation,whichweresignificantlyinhibitedbyJuDancapsuleinadose-dependentmanner.Conclusion:AngⅡmaybeinvolvedintheinitiationandprogressionofcardiovasculardiseasesbyinjuringvascularendotheliumdirectlyandcausingendothelialdysfun