外源性睾酮对雄性小鼠心功能和心脏衰老的影响  

The effects of exogenous testosterone on cardiac function and myocardial senescence in male mice

作　　者：朱桂平[1] 张莉[1] 周玉良[1] 李博维[1] 林忠伟[1] 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

出　　处：《国际心血管病杂志》2016年第6期369-374,共6页International Journal of Cardiovascular Disease

基　　金：广东省公益研究与能力建设专项资金(2014A020212305);广东药学院附属第一医院院内课题

摘　　要：目的:探讨外源性睾酮对雄性小鼠心功能和心脏衰老的影响。方法:15个月龄C57/BL6雄性小鼠分为4组:安慰剂组、睾酮组、沉默信息调节因子1(Sirt1)抑制剂EX-527组(EX-527组)和睾酮+EX-527组,每组7只。干预3个月后超声心动图检测小鼠心功能指标,ELISA法检测小鼠血清睾酮浓度,分离小鼠左心室,组织化学染色法检测衰老相关β-半乳糖苷酶(SA-β-gal),Western blot检测心肌组织B型利钠肽(BNP)、Sirt1蛋白表达水平,实时定量RT-PCR检测心肌组织肌球蛋白重链(MYH)6、MYH7、肌浆网钙ATP酶2(SERCA2)和α-肌动蛋白1(ACTA1)mRNA表达水平。结果:睾酮组及睾酮+EX-527组血清睾酮水平较安慰剂组及EX-527组明显升高(P均<0.05)。与安慰剂组相比,睾酮组SA-β-gal染色阳性面积比例明显减少[(17.13±7.12)%对(35.88±10.74)%,P<0.05],BNP蛋白表达水平、MYH7和ACTA1 mRNA表达水平明显降低(P均<0.05),Sirt1蛋白表达水平、MYH6和SERCA2 mRNA表达水平明显升高(P均<0.05)。EX-527组和睾酮+EX-527组上述各指标与安慰剂组相比无统计学差异,与睾酮组相比有显著性差异(P均<0.05)。超声心动图结果示各组左室舒张末期内径、室间隔厚度、左室后壁厚度、左室缩短分数、左室射血分数及E/A值无显著性差异(P均>0.05)。结论:外源性睾酮可能通过Sirt1途径延缓雄性小鼠心肌细胞衰老,改善心衰相关的基因表达异常。Objective：To investigate the effects of exogenous testosterone on cardiac function and myocardial senescence in male mice. Methods：Twenty-eight 15-month-old male C57/BL6 mice were divided into 4 experimental groups：placebo group,testosterone group,silent information regulator 1（SIRT1）inhibitor EX-527 group（EX-527 group）and testosterone＋EX-527 group.Echocardiography was performed under anesthesia after treatment for 3 months.ELISA was used to detect the serum concentration of testosterone.Senescence associated β galactosidase（SA-β-gal）of left ventricular myocardium was measured by histochemical staining.Western blot was used to estimate the protein expression of B-type natriuretic peptide（BNP）and Sirt1,while real-time RT-PCR was used to assay the mRNA expression of myosin heavy chain（MYH）6、MYH7、sarcoendoplasmic reticulum Ca^（2＋）ATPase 2（SERCA2）andα-skeletal actin（ACTA1）. Results：Serum testosterone levels in testosterone groupand testosterone＋EX-527 group were significantly higher than those in placebo group and EX-527 group（all P〈0.05）.Compared with the placebo group,the proportion of SA-β-gal positive areas,protein expression of BNP,and mRNA expression of MYH7 and ACTA1 were significantly decreased,while the protein expression of Sirt1,and mRNA expression of MYH6 and SERCA2 were significantly increased in testosterone group（all P〈0.05）.These indexes in both EX-527 group and testosterone＋EX-527 group had no significant difference as compared with placebo group,but had significant differences as compared with testosterone group（P〈0.05）.Echocardiography results such as left ventricular end diastolic diameter（LVEDd）,interventricular septal thickness（IVST）,posterior wall thickness（PWT）,left ventricular fractional shortening（LVFS）、left ventricular ejection fractions（LVEF）and E/A value had no significant difference in each gourp（all P〉 0.05）. Conclusion：Exogenous testosterone may retard the process of myocardial senes

关 键 词：衰老 睾酮 心功能不全 沉默信息调节因子1 

分 类 号：R541[医药卫生—心血管疾病]