睾酮对亚急性衰老小鼠下丘脑的影响及其机制

目的观察低刘量睾酮对小鼠下丘脑衰老的影响及其可能的调控机制。方法将24只健康雄性C57小鼠随机分为3组:D-半乳糖+睾酮治疗组(治疗组)、D-半乳糖组和正常对照组,每组8只。用药5个月后分离小鼠下丘脑组织,制备石蜡切片,测定小鼠下丘脑衰老相关性β-半乳糖苷酶(SA-β-Gal)染色情况,用免疫组织化学法检测p16~(INK4a)蛋白的表达水平。结果与正常对照组比较,D-半乳糖组小鼠体重降低(P<0.05),下丘脑SA-β-Gal染色阳性细胞率和p16~(INK4a)蛋白阳性细胞率明显升高(P<0.05);与D-半乳糖组比较,治疗组小鼠体重增加(P<0.05).下丘脑SA-β-Gal染色阳性细胞率和p16~(INK4a)蛋白阳性细胞率明显降低(P<0.05)。结论低剂量睾酮可能通过改变p16~(INK4a)的表达而发挥抗下丘脑细胞衰老的作用。

The effects of testosterone on the hypothalamus of the subacute aging mice and the mechanisms

Objective To observe the effect of low dose testosterone intervention on the expression of β-galactosidase and p16~(INK4a) in the hypothalamus of the aging mouse induced by D-galactose. Method Twenty-four C57 male mice were randomly divided into 3 groups: D-galactose+testos-terone group (n=8) treated with testosterone 5 mg/kg per 2 weeks intramuscular injection and D-galactose 100 mg/kg per day subcutaneous injection in back;D-galactose group (n = 8) treated with D-galactose 100 mg/kg per day subcutaneous injection in back;normal control group (n = 8) treated with physiological saline per day subcutaneous injection in back. The activity of β-galacto-sidase and the expression of p16~(INK4a) in hypothalamus were determined after treatmemt for 5 months. Results Compared with the normal control group,in D-galactose group,the mice showed weight loss,hypothalamus SA-β-Gal staining positive cells and p16~(INK4a) protein positive cells were significantly increased. Compared with the D-galactose group,the mice in D-galactose+testoster-one treatment group showed weight gain, hypothalamus SA-β-Gal staining positive cells and p16~(INK4a) protein positive cells were significantly decreased. Conclusions Low dose testosterone could attenuate the aging of hypothalamus by reducing the expression of p16~(INK4a).