Nogo-B介导线粒体活性氧生成在小鼠血管重构过程中的作用机制  

Mechanisms for Nogo-B mediating mitochondrial reactive oxygen species generation during vascular remodeling in mice

作　　者：杨维维[1] 黄晓莉[2] 李帅 马健[2] 方宁远[3] Yang Weiwer;Huang Xiaoli;Li Shuai;Ma Jian;Fang Ningyuan(Department of Geriatrics.Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine.Shunghai 200127,China;Department of Cardiology.Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University,Shanghai 200233.China;Deparment of General Medicine.Renji Hospilal Affiliated to Shanghai Jiaolong Universilry School of Medicine.Shanghai 200127,China)

机构地区：[1]上海交通大学医学院附属仁济医院老年科,200127 [2]上海交通大学附属第六人民医院心内科,200233 [3]上海交通大学医学院附属仁济医院全科医学科,200127

出　　处：《中华老年医学杂志》2021年第12期1574-1577,共4页Chinese Journal of Geriatrics

基　　金：国家自然科学基金(81300177、81400354、81770282)

摘　　要：目的探讨Nogo-B对小鼠血管平滑肌细胞(VSMCs)线粒体活性氧生成(m-ROS)和血管重构的影响, 并进一步明确Nogo-B通过干预ATP合酶进而干预m-ROS生成的分子机制。方法构建小鼠血管重构模型后检测血管平滑肌细胞Nogo-B表达, 在体实验分组:AAV-NC+Control组及AAV-NC+血管紧张素Ⅱ(AngⅡ)组, AAV-Nogo-B+Control组及AAV-Nogo-B+AngⅡ组, 每组10只;细胞培养分为对照组和Nogo-B过表达组(Ad-Nogo-B组)。体外实验采用AngⅡ诱导培养基刺激VSMCs后测定细胞内Nogo-B表达;在体实验于VSMCs中过表达Nogo-B再予AngⅡ刺激, 测定细胞m-ROS生成、组织纤维化指标及线粒体功能;明确Nogo-B与m-ROS生成的调节关系;探讨Nogo-B通过干预ATP合酶/m-ROS生成通路进而干预血管重构的分子机制。结果与对照组比较, AngⅡ诱导后的VSMCs内Nogo-B的表达降低, 0.36±0.13比1.00±0.13(t=8.44, P<0.05);血管重构过程中VSMCs内的m-ROS生成、纤维化指标及线粒体功能受损增加(P<0.05), 而过表达Nogo-B可减少m-ROS生成、纤维化指标及线粒体功能受损(P<0.05);VSMCs内Nogo-B正向调节ATP合酶表达, Ad-NC+AngⅡ组与Ad-Nogo-B+AngⅡ组比较为0.49±0.17比0.86±0.14(t=-3.97, P<0.05), 能够减少m-ROS生成, Ad-NC+AngⅡ组与Ad-Nogo-B+AngⅡ组比较为3.26±0.57比1.28±0.34(t=7.18, P<0.05), 而Nogo-B减轻VSMCs氧化应激损伤的作用可被Oligomycin特异性抵消。结论 Nogo-B通过调节ATP合酶介导m-ROS生成进而参与血管重构过程。Objective To investigate the role of Nogo-B in mitochondrial reactive oxygen species(m-ROS)production and vascular remodeling in vascular smooth muscle cells(VSMCs).and to further clarify the molcular mechanism for Nogo-B in m-ROS production via regulating ATP synthase expression.Methods A mouse model of vascular remodeling was established.The expression of Nogo-B in mouse smooth muscle cells was detected.Forty mice were divided into the AAV-NC+control,AAV-NC+angiotensin Ⅱ(AngⅡ)。AAV-Nogo-B+control and AAV-Nogo-B+AngⅡ groups(n=10 for each group).VSMCs cultured in vitro were divided into the control group and the Nogo B overexpression group(Ad Nogo B).The expression of Nogo-B in VSMCs in vitro stimulated with AngⅡ was detected.Through experiments conducted in vivo.Nogo-B was overexpressed in VSMCs.then VSMCs were stimulated with AngⅡand m-ROS production.tissue fibrosis and mitochondrial function were examined.The regulatory efcts of Nogo-B on m-ROS production were explored.Molecular mechanisms for NoGO-B in vascular remodeling via regulating ATP synthase/m-ROS production were examined.Results Compared with the control group,the expression of Nogo-B was decreased in VSMCs treated with AngⅡ(0.36±0.13 us.1.00±0.13.t=8.44.P<0.05).The.production of m-ROS,fibrosis and mitochondrial dysfunction were increased in VSMCs during vascular remodeling(P<0.05),while overexpression of Nogo B significantly reduced m-ROS production.fibrosis and mitochondrial dysfunction(P<0.05).ATP synthase expression in VSMCs was positively regulated by Nogo B.ATP synthase expression was higher in the AAV-Nogo-B+AngⅡ group than in the AAV-NC+AngⅡ group(0.86±0.14 us.0.49±0.17.1=-3.97,P<0.05).The production of m-ROS was reduced by Nogo-B and was lower in the AAV-Nogo-B+AngⅡ group than in the AAV-NC+AngⅡ group(1.28±0.34 us.3.26±0.57.t=7.18,P<0.05).Meanwhile,the ability of Nogo-B to mitigate the deleterious efects of oxidative stress in VSMCs could be offset by oligomyein.Conclusions Nogo B participates in vascular remodelin

关 键 词：Nogo-B 线粒体 肌 平滑 血管 

分 类 号：R543[医药卫生—心血管疾病]