PPARα/NO在血管紧张素Ⅳ诱导血管平滑肌细胞增殖中的作用  

Role of Peroxisome Proliferator-activated Receptor-α/Nitric Oxide in Induction of Proliferation of Vascular Smooth Muscle Cells by Angiotensin Ⅳ

作　　者：王全华[1] 陈加飞[1] 承欧梅[1] 吴芹[2] 蒋青松[1] 

机构地区：[1]重庆医科大学药理学教研室,重庆400016 [2]遵义医学院药理教研室,贵州遵义563003

出　　处：《中国生物制品学杂志》2011年第6期685-688,共4页Chinese Journal of Biologicals

基　　金：重庆市自然科学基金计划项目(CSTC;2010BB5108)

摘　　要：目的探讨过氧化物酶体增殖物激活受体α(Peroxisome proliferator-activated receptorα,PPARα)/一氧化氮(Ni-tric oxide,NO)信号通路在血管紧张素Ⅳ(AngiotensinⅣ,AngⅣ)诱导血管平滑肌细胞(Vascular smooth muscle cells,VSMCs)增殖中的作用。方法体外培养大鼠VSMCs,将细胞分为6组:对照组(只加培养基)、AngⅣ组、AngⅣ+非诺贝特(Fenofibrate,FF)组、AngⅣ+FF+MK 886组、AngⅣ+L-arg组和AngⅣ+L-arg+L-NAME组,MTT法检测细胞的增殖;BCA法测定细胞总蛋白含量;Real-time PCR法检测细胞中PPARα和eNOS基因mRNA的表达;Western blot法检测细胞中PPARα蛋白的表达;比色法和硝酸还原法分别检测细胞培养上清中一氧化氮合酶(Nitric oxide synthase,eNOS)活性和NO浓度。结果 0.1 nmol/L AngⅣ可诱导VSMCs增殖,增加细胞总蛋白含量,PPARαmRNA及蛋白表达明显降低,eNOS基因mRNA表达减少,细胞上清中NOS活性及NO浓度降低;FF和L-arg可逆转AngⅣ的上述作用,并被相应的阻断剂(MK 886和L-NAME)抑制。结论 AngⅣ诱导VSMCs的增殖作用可能与PPARα/NO信号通路受损有关。Objective To investigate the role of peroxisome proliferator-activated receptor-α（PPARα）/nitric oxide（NO） pathway in induction of proliferation of vascular smooth muscle cells（VSMCs） by angiotensin Ⅳ（AngIV）.Methods Rat VSMCs were cultured in vitro and divided into six groups,then added with medium（control）,Ang Ⅳ,Ang Ⅳ＋ fenofibrate（FF）,Ang Ⅳ ＋ FF ＋MK 886,Ang Ⅳ＋L-arg and AngⅣ＋L-arg＋L-NAME respectively and determined for proliferation level by MTT method,for total cellular protein content by BCA method,for expressions of PPARα and eNOS mRNAs by real-time PCR,for expression of PPARα protein by Western blot,for nitric oxide synthase（NOS） activity in culture supernatant by colorimetry,and for NO concentration by nitrate reduction method.Results The Ang Ⅳ at a concentration of 0.1 nmol/L induced the proliferation of VSMCs,increased the total cellular protein content,decreased the expressions of PPARα mRNA and protein and eNOS mRNA as well as the NOS activity and NO concentration in cell culture supernatant.However,FF and L-arg reversed the above-mentioned effects of Ang Ⅳ,which were inhibited by the corresponding antagonists MK 886 and L-NAME respectively.Conclusion The proliferation of VSMCs induced by Ang Ⅳ might be associated with the damage of PPARα/NO signal transduction pathway.

关 键 词：肌细胞 平滑肌 细胞增殖 血管紧张素类 一氧化氮 过氧化物酶体增殖物激活受体Α 

分 类 号：Q253[生物学—细胞生物学]