高剂量缬沙坦对卵巢摘除后自发性高血压大鼠左心室肥厚的作用  

Effect of high-dose valsartan on left ventricular hypertrophy in ovariectomized spontaneously hypertensive rats

作　　者：丁虹 李宁荫[1] 张翔 张盼盼 余静[1] DING Hong;LI Ning-ying;ZHANG Xiang;ZHANG Pan-pan;YU Jing(Department of Cardiology,Lanzhou University Second Hospital,Lanzhou Gansu 730030,China)

机构地区：[1]兰州大学第二医院心内科,甘肃兰州730030

出　　处：《中华高血压杂志》2019年第9期838-844,共7页Chinese Journal of Hypertension

基　　金：国家自然科学基金项目(8167020411);兰州大学第二医院院内课题(CY2017-QN08)

摘　　要：目的探讨缬沙坦(Val)对卵巢摘除术(OVX)自发性高血压大鼠(SHR)左心室结构与功能的作用及其与体内氧化应激水平变化的关系。方法 12周龄SPF级雌性SHR随机分为卵巢摘除手术组(OVX组,n=30)和假手术组(Sham组,n=30),分别给予OVX或假手术干预。术后,OVX组随机分为OVX对照组(n=12)和OVX+缬沙坦组(OVX+Val组,n=12),Sham组随机分为Sham对照组(n=13)和Sham+缬沙坦组(Sham+Val组,n=14),分别给予等体积蒸馏水和缬沙坦30mg/(kg·d)。术后4周放射免疫法测定性激素水平。缬沙坦干预12周后行超声心动图及有创血流动力学检测左心室功能;酶联免疫吸附试验法检测血清超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH)、8-羟基脱氧鸟苷水平(8-OhdG)。结果 OVX和缬沙坦对舒张末期室间隔厚度(IVSTd)、收缩末期室间隔厚度(IVSTs)、舒张末期左心室后壁厚度(LVPWTd)和左心室舒张末期内径(LVEDD)的影响有交互作用(P<0.05),OVX术后IVSTd[(1.2±0.1)比(1.1±0.1)mm]、IVSTs[(2.0±0.2)比(1.7±0.1)mm]、LVPWTd[(1.2±0.1)比(1.1±0.2)mm]和LVEDD[(7.1±0.2)比(6.0±0.5)mm]较Sham组升高(均P<0.05);缬沙坦治疗后OVX+Val组较OVX对照组IVSTd、IVSTs、LVPWTd和LVEDD降低[分别为(0.9±0.1)比(1.2±0.1)、(1.4±0.2)比(2.0±0.2)、(0.9±0.1)比(1.2±0.1)和(4.8±0.2)比(7.1±0.2)mm,均P<0.05]。OVX和缬沙坦对左心室收缩末压(LVESP)、左心室舒张末压(LVEDP)、左心室压力上升和下降最大速度(±dp/dt)的影响有交互作用(均P<0.05)。与Sham对照组比较,OVX对照组LVESP[(56.3±1.9)比(72.1±1.5)mm Hg]和±dp/dt[(1202.8±152.0)比(2879.2±287.2)mm Hg/s、(1651.1±37.2)比(3482.7±119.5)mm Hg/s]降低,LVEDP升高[(6.8±0.4)比(6.4±1.1)mm Hg;均P<0.05]。缬沙坦治疗后,OVX+Val组较OVX对照组LVESP [(135.2±2.9)比(56.3±1.9)mm Hg]和±dp/dt [(4730.3±250.2)比(1202.8±152.0),(5049.3±247.2)比(1651.1±37.2)mm Hg/s]升高,LVEDP降低(均P<0.05)。OVX对照组较Sham对照组GSH、SOD降低,8-OHdG升高,缬沙坦Objective To investigate the effect of valsartan on improving left ventricular structure and function and the association with cardiac oxidative stress in ovariectomized spontaneously hypertensive rats(SHR).Methods Twelve-week aged specific pathogen free female SHR were randomly divided into ovariectomy group(OVX,n=30)and sham operation group(Sham,n=30).After ovariectomy or sham operation intervention,the rats in OVX group were randomly divided into OVX control group(n=12)and OVX+valsartan group(OVX+Val,n=12),and rats in Sham group were randomly divided into Sham control group(n=13,distilled water)and Sham+valsartan group(Sham+Val,n=14,valsartan).Rats in OVX+Val and Sham+Val groups were given Val with 30 mg/(kg·d),while rats in OVX control and Sham control group received the same volume of double-distilled water.After 4 weeks of operation,serum levels of testosterone and estradiol were measured by radioimmunoassay.Left ventricular structure and function were assessed by hemodynamic and echocardiography parameters after treated with valsartan for 12 weeks.Superoxide dismutase(SOD),glutathione peroxidase(GSH)and 8-hydroxydeoxyguanosine(8-OHdG)were detected by enzyme-linked immunosorbent assay(ELISA)analysis.Results There was an interaction between ovariectomy and valsartan on interventricular end-diastolic septum thickness(IVSTd),end-systolic interventricular septum thickness(IVSTs),left ventricular end-diastolic posterior wall thickness(LVPWTd)and left ventricular end diastolic diameter(LVEDD)(P<0.05).Ovariectomy had a negative effect on IVSTd[(1.2±0.1)vs(1.1±0.1)mm],IVSTs[(2.0±0.2)vs(1.7±0.1)mm],LVPWTd[(1.2±0.1)vs(1.1±0.2)mm]and LVEDD[(7.1±0.2)vs(6.0±0.5)mm](P<0.05)compared with Sham+control group,while valsartan could reverse IVSTd,IVSTs,LVPWTd and LVPWTs((0.9±0.1)vs(1.2±0.1)mm,(1.4±0.2)vs(2.0±0.2)mm,(0.9±0.1)vs(1.2±0.1)mm and(4.8±0.2)vs(7.1±0.2)mm;all P<0.05)There was a interaction between ovariectomy and valsartan on LVESP,LVEDP and±dp/dt(P<0.05).Compared with Sham+control group,LVESP[(56.3±

关 键 词：绝经 左心室肥厚 氧化应激 缬沙坦 

分 类 号：R544.1[医药卫生—心血管疾病] R-332[医药卫生—内科学]