Physiological doses of testosterone retards murine cardiomyocyte aging via androgen receptor independent pathway / 中华老年医学杂志

ABSTRACT

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 groupsthe 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 Physiological doses of testosterone can retard cardiomyocyte aging via androgen receptor independent pathways.