睾酮改善D-半乳糖诱导的衰老大鼠主动脉血管结构和功能的机制探讨  

Testosterone improved the aortic vascular structure and function of rats in D-galactose-induced rat model of aging

作　　者：任军伟[1] 刘金晶[1] 钱卫[1] 张晨[1] 刘磊[2] 闫长栋[2] 

机构地区：[1]徐州医学院临床医学系,江苏徐州221004 [2]徐州医学院生理学教研室,江苏徐州221004

出　　处：《现代医学》2015年第7期822-826,共5页Modern Medical Journal

基　　金：江苏省大学生实践创新训练计划项目(2012JSSPITP1848)

摘　　要：目的:初步探讨睾酮对D-半乳糖诱导的衰老大鼠血管结构和功能的影响及机制。方法:取3月龄大鼠颈背部皮下注射D-半乳糖(D-galactose,D-gal)125 mg·kg-1·d-1,连续6周,制备衰老大鼠模型。衰老模型大鼠颈背部皮下注射不同剂量(0.01、0.10、1.00 mg·kg-1·d-1)外源性睾酮,持续4周。ELISA法测定大鼠血浆睾酮(Testosterone)含量;HE和Masson染色方法观察主动脉形态和胶原纤维含量的变化;离体主动脉血管灌流方法观察血管舒张功能以及给予内皮源性一氧化氮合酶(endothelial nitric-oxide synthase,e NOS)阻断剂L-硝基-精氨酸甲酯(L-NAME)后血管的舒张功能变化;蛋白质印迹法检测主动脉血管e NOS蛋白含量的变化。结果:与对照组相比,D-gal组血浆睾酮水平明显降低,外源性补充睾酮后D-gal组大鼠血浆睾酮水平明显升高。形态学观察显示,对照组大鼠主动脉管壁较薄,平滑肌细胞排列整齐,D-gal组大鼠管壁明显增厚,平滑肌细胞排列不整齐,外源性补充睾酮能改善D-gal组大鼠血管形态学变化。与对照组相比,D-gal组大鼠血管舒张功能明显降低,补充0.10和1.00 mg·kg-1·d-1睾酮明显改善D-gal组大鼠血管舒张功能。与对照组相比,D-gal组大鼠主动脉e NOS蛋白表达明显降低,外源性补充睾酮增加D-gal组大鼠主动脉e NOS蛋白的表达。e NOS抑制剂L-NAME能够阻断睾酮引起的血管舒张作用。结论:衰老导致大鼠血浆睾酮水平下降,进而引起血管舒张功能降低及形态改变,给予外源性睾酮可通过增加主动脉内皮细胞e NOS的表达,改善主动脉血管的舒张功能并逆转血管形态学的改变,从而起到抗血管老化作用。Objective： To investigate the influence of testosterone on vascular structure and function of D-galactose-induced rat model of aging and its mechanism. Methods： Rats were given subcutaneous injection of125 mg· kg^-1·d^-1 D-galactose for 6 weeks manufacturing in D-galactose-induced rat model of aging,then injected with exogenous testosterone in different doses（ 0. 01,0. 10,1. 00 mg ·kg^-1·d^-1） for 4 weeks in the same way. The content of plasma testosterone of the rats were determined with ELISA method. The changes of vascular structure and content of collagen were observed by HE staining and Masson staining. The vascular diastolic function and its changes were observed respectively by the method of isolated aortic perfusion and adding L-NAME,an endothelial nitric-oxide synthase（ e NOS） inhibitor. Results： Compared to control group,plasma concentration of testosterone in D-galactose group was decreased,while it was increased in testosterone group after treatment with testosterone. Morphology showed that the aorta wall of D-galactose group was thick,and smooth muscle cells arranged in disorder,and the relative content of collagen fibers increased significantly in comparison to control group,while aged aortic morphologic change in aging rat model was ameliorated with testosterone treatment.Additionally,compared to control group,diastolic function in D-galactose group was decreased,while improved after supplementing the testosterone of 0. 10 and 1. 00 mg ·kg^-1·d^-1respectively. Furthermore,the relaxation could be blocked by L-NAME,an e NOS inhibitor. Western blotting analysis showed that the expression of e NOS was obviously higher in the testosterone（ 0. 10,1. 00 mg·kg^-1·d^-1） treated groups than that in the D-galactose group. Conclusion：Aging results in the decrease of plasma testosterone in rats,and then dscreases the vascular diastolic function and changes the morphology. Giving exogenous testosterone can increase the expression of e NOS of aortic endothelial cells,improve vascular d

关 键 词：睾酮 老化 血管舒张 胶原纤维 内皮源性一氧化氮合酶 大鼠 

分 类 号：R331.32[医药卫生—人体生理学]