生理剂量睾酮通过非雄激素受体依赖的机制延缓心肌细胞衰老  

Physiological doses of testosterone retards murine cardiomyocyte aging via androgen receptor independent pathway

作　　者：张莉[1] 吴赛珠[2] 雷达[1] 

机构地区：[1]广东药学院附属第一医院心内科,广州510080 [2]南方医科大学附属南方医院心内科

出　　处：《中华老年医学杂志》2014年第7期788-791,共4页Chinese Journal of Geriatrics

基　　金：国家973计划项目（2007CB507404）

摘　　要：目的 探讨睾酮治疗是否通过其经典的雄激素受体（AR）途径影响心肌细胞衰老的发生. 方法 雄性C57BL/6J鼠和睾丸女性化鼠（Tfm）分为正常组（8只）、去势组（8只）、Tfm组（7只）、去势＋睾酮（T）组（8只）、Tfm＋T组（8只）.分离左心室心肌细胞测定超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量及测定p16 INK4a和去磷酸化Rb蛋白表达量. 结果 与正常组比较,去势组和Tfm组SOD活性减弱[（16.55±1.18） U/ml、（17.30±1.32） U/ml比（21.57±2.21）U/ml,P＜0.05];MDA含量增加[（7.78±1.27） μmol/L、（6.52±0.82） μmol/L比（3.48±0.70） μmol/L,P＜0.01];p16INK4a（0.37±0.08、0.45±0.06比0.14±0.02）和去磷酸化Rb（0.74±0.05、0.79±0.08比0.40±0.05）蛋白表达水平上调（P＜0.05）.与去势组比较,去势＋T组SOD活性[（23.00±0.58）U/mD增加（P＜0.01）;MDA含量[（2.63±0.90）μmol/L]、p16INK4a（0.13±0.03）和去磷酸化Rb（0.45±0.05）蛋白表达水平均下降（P＜0.05）.与Tfm组比较,Tfm＋T组SOD活性增加,MDA含量、p16INK4a和去磷酸化Rb蛋白表达水平下降（P＜0.05）.去势＋T组与Tfm＋T组比较差异无统计学意义（P＞0.05）. 结论 生理剂量睾酮治疗通过非AR依赖的机制延缓心肌细胞衰老.Objective To explore whether physiological doses of testosterone therapy can modulate cardiomyocyte aging via classical androgen receptor （AR） dependent pathways.Methods Male C57BL/6J mice and testicular feminized （Tfm） mice were divided into five experimental groups：the control group （n=8）,the castrated group （n=8）,the Tfm group （n=7）,the testosterone treated castrated group （n=8）,and the testosterone-treated Tfm group （n =8）.After isolation of cardiomyocytes from the left ventricle,the activity of superoxide dismutase （SOD） and the amount of malondialdehyde （MDA） were measured using colorimetry,and the expression of the p16INK4a and retinoblastoma （Rb） proteins was detected by Western blotting.Results Compared with the control group,the activity of SOD in the castrated group and the Tfm group declined [（16.55±1.18） U/ml,（17.30±1.32） U/ml vs.（21.57±2.21）U/ml,P＜0.05）],the amount of MDA increased [（7.78±1.27）μmol/L,（6.52±0.82）μmol/L vs.（3.48±0.70）μmol/L],P＜0.01,and the expression of both the p16INK4aand Rb proteins increased [（0.37±0.08）,（0.45±0.06） vs.（0.14±0.02）,forp16INK4a,P＜0.05; （0.74±0.05）,（0.79±0.08） vs.（0.40±0.05）,for Rb,P＜0.05].Compared with the castrated group,the activity of SOD in the testosterone treated castrated group increased [（23.00±0.58）U/ml vs.（16.55±1.18） U/ml,P＜0.01],the amount of MDA decreased [（2.63±0.90） μmol/L vs.（7.78±1.27） μmol/L,P＜0.01],and the p16INK4a and Rb proteins were both downregulated （0.13 ± 0.03 vs.0.37± 0.08）,for p16INK4a,P＜0.05; （0.45 ±0.05） vs.（0.79±0.08）,for Rb P＜0.05.Compared with the Tfm group,the activity of SOD in testosterone-treated Tfm group increased,the amount of MDA decreased,and the p16IN4a and Rb proteins were both downregulated （P＜ 0.05）.No significant differences in these markers were detected between the testosterone-treated castrated group and the testosterone-treated Tfm group.Conclusions Ph

关 键 词：衰老 肌细胞 心脏 睾酮 受体 雄激素 

分 类 号：R965[医药卫生—药理学]