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	视黄醇X受体激动剂蓓萨罗丁对自发性高血压大鼠心肌肥厚与心脏功能的影响和机制; Effect of retinoid X receptor agonist bexarotene on myocardial hypertrophy and cardiac function in spontaneously hypertensive rats
	林晓燕 ; 阮琴韵 ; 祝江 ; 许昌声 ; 曾锦章 ; 柴大军
	2014-11-15
关键词	视黄醇X受体 自发性高血压大鼠 心肌肥厚 Retinoid X receptor Spontaneously hypertensive rats Hypertrophy
英文摘要	目的探讨视黄醇X受体(rXr)激动剂蓓萨罗丁(bEX)对自发性高血压大鼠(SHr)心肌肥厚和心脏功能的影响及其分子机制。方法24只SHr随机分为SHr组;SHr+bEX 30 Mg/(kg·d)(bEX30)组;SHr+bEX100Mg/(kg·d)(bEX100)组,每组8只。8只与SHr周龄相匹配的WISTAr-kyOTO(Wky)大鼠作为对照组。大鼠在4周龄采用灌胃法开始药物干预至16周末;采用尾袖法测定动物血压,心脏超声评定大鼠心脏结构和功能,称重测定大鼠体质量和左心室质量(lVM);放射免疫法测定血浆及心肌组织中血管紧张素Ⅱ(AngⅡ)含量,苦味酸天狼猩红染色结合图像分析测定心肌外膜胶原容积;免疫杂交检测心肌组织中rXrα表达水平。结果 16周龄SHr血压高于Wky大鼠[(191.8±3.1)/(132.7±5.5)比(120.5±5.0)/(89.6±3.2)MM Hg,P<0.05],但SHr、SHr+bEX30及SHr+bEX100 3组间血压水平差异无统计学意义;与Wky组比较,SHr组心脏lVM、左心室质量指数(lVMI)、左心室后壁厚度(lVPWT),室间隔厚度(IVST)升高(均P<0.05);左心室等容舒张时间(IVrT)延长,二尖瓣环E峰峰速度(EA)、A峰峰速度(AA)及EA/AA明显减低;与SHr组相比,SHr+bEX30及SHr+bEX100组的心脏lVM[(0.78±0.02),(0.67±0.01)比(0.90±0.04)g]、lVMI[(2.66±0.06),(2.28±0.03)比(2.95±0.10)g/kg]、lVPWT、IVST降低(均P<0.05),SHr+bEX100组IVrT明显缩短,EA、AA及EA/AA增加;SHr组血浆AngⅡ[(79.19±6.25)比(48.62±1.91)ng/l]及心肌组织AngⅡ[(85.10±3.48)比(69.94±4.01)ng/l]水平明显高于Wky组;SHr+bEX30及SHr+bEX100两组大鼠血浆及心肌组织的AngⅡ水平与SHr组差异无统计学意义;SHr组心肌外膜胶原容积分数(CVf)高于Wky组[(13.2±1.8)%比(4.1±0.7)%;P<0.05];蓓萨罗丁可显著降低SHr心肌外膜CVf[SHr+bEX30组(8.1±0.8)%比SHr组(13.2±1.8)%,P<0.05];SHr+bEX100组降低更为明显[(5.8±0.8)%];SHr组心肌组织中的rXrα蛋白水平较Wky明显降低,rXr激动剂蓓萨罗丁可增加SHr心肌rXrα蛋白表达(P<0.05)。结论 rXr激动剂蓓萨罗丁通过调控心肌胶原含量逆转SHr心肌肥厚,大剂量时还可以改善心脏舒张功能,且这些效应均不依赖于血压变化。; Objective To explore the effect and related molecular mechanisms of retinoid X receptor(RXR)agonist bexarotene(Bex)on myocardial hypertrophy and cardiac function in spontaneously hypertensive rats(SHR).Methods A total of 24four-week-old SHR were randomized into 3groups and treated with 30mg/kg Bex(SHR+Bex30),100mg/kg Bex(SHR+Bex100)and vehicle(SHR)once a day for 12 weeks,respectively,while 8agematched Wistar-Kyoto(WKY)rats were served as control group.Echocardiography was performed to detect cardiac structure and function parameters.Blood pressure was measured with BP98 Atail cuff system.Body mass,heart mass and left ventricle mass(LVM)were monitored.Angiotensin(Ang)Ⅱ level was determined by radio immunoassay.Picrosirius staining was performed to determine myocardial epicardial collagen volume.RXRαprotein level was measured with immunoblotting.Results Compared with WKY rats,blood pressure of SHR was significantly increased[SHR vs WKY:systolic blood pressure:(191.8±3.1)vs(120.5±5.0)mm Hg,P<0.05;diastolic blood pressure(132.7±5.5)vs(89.6±3.2)mm Hg,P<0.05].Blood pressures between SHR,SHR+Bex30and SHR+Bex100group were not significantly different.LVM,left ventricular mass index(LVMI),thickness of left ventricular posterior wall(LVPWT)and interventricular septal thickness(IVST)of SHR were greatly increased compared to those of WKY rats(all P<0.05).Compared with WKY,echocardiographic analysis showed that isovolumic relaxation time(IVRT)was significantly increased in SHR,while Ea,Aa and Ea/Aa were decreased.Compared to SHR group,LVM [(0.78±0.02),(0.67±0.01)vs(0.90±0.04)g],LVMI[(2.66±0.06),(2.28±0.03)vs(2.95±0.10)g/kg],LVPWT,IVST in SHR+Bex30and SHR+Bex100groups were significantly decreased(all P<0.05).Meanwhile,Ea,Aa and Ea/Aa increased and IVRT decreased in SHR+Bex100group.Compared with WKY,the level of AngⅡ in plasma[(79.19±6.25)vs(48.62±1.91)ng/L]and heart tissue[(85.10±3.48)vs(69.94±4.01)ng/L]of SHR was significantly increased(P<0.05).Bex showed no effect on Ang Ⅱ.Myocardial epicardial collagen volume fraction(CVF)of heart tissue was significantly higher in SHR than in WKY [(13.2±1.8)% vs(4.1±0.7)%,P<0.05],but CVF was decreased by Bex treatment(SHR+Bex30vs SHR:(8.1±0.8)% vs(13.2±1.8)%;SHR+Bex100vs SHR:(5.8±0.8)% vs(13.2±1.8)%,P<0.05].Compared to WKY,RXRαexpression in SHR was significantly dereased,which could be increased by Bex(P<0.05).Conclusion RXRαagonists Bex can reduce left ventricular hypertrophy of SHR by regulating collagen content.High dose of Bex can even improve cardiac diastolic function.These effects of Bex are not depended on blood pressure control.; 福建省自然基金资助项目(2013J01300)
语种	zh_CN
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/123495]
专题	药学院－已发表论文
推荐引用方式 GB/T 7714	林晓燕,阮琴韵,祝江,等. 视黄醇X受体激动剂蓓萨罗丁对自发性高血压大鼠心肌肥厚与心脏功能的影响和机制, Effect of retinoid X receptor agonist bexarotene on myocardial hypertrophy and cardiac function in spontaneously hypertensive rats[J],2014.
APA	林晓燕,阮琴韵,祝江,许昌声,曾锦章,&柴大军.(2014).视黄醇X受体激动剂蓓萨罗丁对自发性高血压大鼠心肌肥厚与心脏功能的影响和机制..
MLA	林晓燕,et al."视黄醇X受体激动剂蓓萨罗丁对自发性高血压大鼠心肌肥厚与心脏功能的影响和机制".(2014).

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