内质网应激参与自发性高血压大鼠血管老化的机制研究  

Mechanism of endoplasmic reticulum stress involved in vascular aging in spontaneously hypertensive rats

作　　者：许甜甜 李书国[1] 邵文[1] XU Tiantian;LI Shuguo;SHAO Wen(First College of Clinical Medical Science,China Three Gorges University,Dept.of Geriatrics,Yichang Central People's Hospital,&Institute of Geriatrics,China Three Gorges University,Yichang 443003,Hubei,China)

机构地区：[1]三峡大学第一临床医学院/宜昌市中心人民医院老年病科/三峡大学老年医学研究所,湖北宜昌443003

出　　处：《武汉大学学报（医学版）》2023年第6期693-698,共6页Medical Journal of Wuhan University

基　　金：湖北省自然科学基金资助项目(编号:2016CFC023)。

摘　　要：目的:探讨内质网应激(ERS)在自发性高血压大鼠(SHR)血管老化过程中的潜在作用及机制。方法:12只3月龄的雄性SHR随机分为实验A、B组,分别以食用淀粉(A组)和硝苯地平40 mg+美托洛尔75 mg灌胃(B组)治疗。3只3月龄雄性SD大鼠为空白对照(C)组,以食用淀粉灌胃治疗。普通饮食喂养9个月,观察各组大鼠血压、心率及一般情况。腹腔注射1%的戊巴比妥钠麻醉后取大鼠的股动脉条备检。HE染色观察各组大鼠股动脉血管形态学特征,实时聚合酶链反应(RT-PCR)及免疫荧光组织化学染色测定CHOP、XBP1、p53、p21表达水平。结果:(1)与A组相比,B组大鼠收缩压下降了约28%、舒张压下降约22%、心率下降约35%,C组血压、心率基本稳定。(2)A组SHR股动脉存在早期血管老化,表现为内皮细胞受损,血管平滑肌细胞迁移,管腔狭窄,内中膜层不均匀增厚;B组与A组相比血管老化减轻,中膜层血管平滑肌细胞迁移显著减少,内中膜厚度显著减小,C组形态学正常。(3)A组大鼠衰老相关基因p53、p21 mRNA及蛋白表达水平较C组显著上调,B组大鼠衰老相关基因表达水平较A组明显下降。(4)A组大鼠ERS相关基因CHOP、XBP1 mRNA及蛋白表达水平较C组显著上调,B组大鼠内质网应激相关基因表达水平较A组明显下降。结论:SHR股动脉存在早期血管老化,机制可能与ERS有关;早期降压治疗可以通过抑制ERS减轻血管老化。Objective:To investigate the potential role and mechanism of endoplasmic reticulum stress(ERS)in the process of vascular aging in spontaneously hypertension rat(SHR).Methods:Twelve 3-month-old male SHRs were randomly divided into experimental groups A and B,treated with edible starch(group A)and nifedipine 40 mg+metoprolol 75 mg(group B)by gavage respectively.Three 3-month-old male Sprague-Dawley(SD)rats were selected as the blank control group(group C),ga-vaged with edible starch.The rats were fed with a normal diet for 9 months,the blood pressure,heart rate,and general conditions of the rats in each group were observed.After anesthesia with 1%pento-barbital sodium by intraperitoneal injection,the femoral artery strips of the rats were taken for examination.HE staining was used to observe the morphological characteristics of the femoral arteries of the rats in each group,the expression levels of CHOP,XBP1,p53,and p21 were determined by realtime polymerase chain reaction(RT-PCR)and immunofluorescence histochemical staining.Results:①Compared with that respectively in group A,the systolic blood pressure decreased by about 28%,the diastolic blood pressure decreased by about 22%and the heart rate decreased by about 35%in group B.The blood pressure and heart rate in group C remained stable.②The early vascular aging was found in the SHRs'femoral artery in group A,which was characterized by endothelial cell damage,vascular smooth muscle cell migration,lumen stenosis,and uneven thickening of the intima-media layer.Compared with the pathologic changes in group A,the aging degree of femoral artery vessels was alleviated,the migration of vascular smooth muscle cell from the media layer to the intima layer was significantly reduced,the thickness of the intima-media layer was significantly decreased in group B,while the morphology of group C was normal.③Compared with those in group C,the mRNA and protein expression levels of aging-related genes p53 and p21 were significantly up-regulated in group A,while the expression

关 键 词：内质网应激 高血压 血管老化 

分 类 号：R544.1[医药卫生—心血管疾病]