雄激素缺乏及外源性睾酮对雄性小鼠心脏衰老的影响  

Effects of androgen deficiency and exogenous testosterone on myocardial senescence of male mice

作　　者：张莉[1,2] 吴赛珠[1] 阮云军[3] 洪雷[1] 赖文岩[1] 

机构地区：[1]南方医科大学南方医院心内科,广州510515 [2]广东省增城市人民医院心内科 [3]广州军区总医院心内科

出　　处：《中华老年心脑血管病杂志》2010年第12期1117-1120,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家"973"计划项目(2007CB507404)

摘　　要：目的探讨雄激素缺乏是否与心脏衰老有关,以及不同剂量丙酸睾酮对心脏衰老的影响。方法雄性C57BL,/6J小鼠32只随机分为正常组(8只)、去势+安慰剂组(去势组,8只)、去势+生理剂量睾酮组(生理剂量组,8只)、去势+大剂量睾酮组(大剂量组,8只)。治疗3个月后测定各组血清睾酮浓度,分离心肌组织荧光实时定量PCR测定端粒长度以及Western b10t测定去磷酸化Rb蛋白表达量。结果与正常组比较,去势组小鼠睾酮明显降低(P<0.01),端粒长度明显缩短(P=0.029),去磷酸化Rb蛋白表达明显增加(P<0.01)。治疗3个月后,与去势组比较,生理剂量组小鼠端粒长度明显延长(P<0.01);去磷酸化Rb蛋白表达明显减少(P<0.05);大剂量组小鼠端粒长度进一步缩短(P<0.05);去磷酸化Rb蛋白表达进一步增加(P<0.01)。结论雄激素缺乏小鼠心肌组织发生衰老,给予生理剂量睾酮可延缓心脏衰老,大剂量睾酮对心脏衰老有促进作用。Objective To determine whether testosterone deficiency is associated with myocardial senescence and to explore the effect of different doses of testosterone propionate replacement on myocardial senescence. Methods Thirty-two male C57BL/6J mice were randomly divided into control group （n = 8）,castrated＋placebo group（castrated group, n = 8）,castrated＋physiological dose of testosterone group （7l = 8） and castrated＋high dose of testosterone group （71 ： 8）. All groups were fed for 3 months. Blood testosterone concentration was measured. Telomere length of myocardium was measured by quantitative PCR and expression of dephosphorylated Rb protein was detected by Western blot. Results Testosterone concentrations were significantly higher in control group than in castrated group （P 〈 0.01） and similar to those in physiological dose of testosterone group. Compared with control group, telomere length was shorter （P= 0. 029） and expression of dephosphorylated Rb protein was up-regulated （P = 0. 001） in myocardial tissues of castrated group. Compared with castrated group, the above changes were ameliora- ted after 3 months of physiological testosterone replacement （P〈 0.05） ,while further exacerba ted after 3 months of high-dose testosterone replacement （P〈 0.05）. Conclusions Testosterone deficiency is associated with myocardial senescence. Physiological dose of testosterone is able to delay myocardial senescence,while high dose of testosterone may exacerbate this process.

关 键 词：雄激素类 睾酮 丙酸 衰老 心肌 DNA结合蛋白质类 端粒 

分 类 号：R541[医药卫生—心血管疾病]