雄性Akt2基因缺失小鼠生殖表型研究

摘要

目的 通过对雄性Akt2基因敲除纯合子小鼠(Akt2-/-)及野生型小鼠(Akt2+/+)基础指标、血清糖脂及性激素水平的评估,探讨Akt2基因缺失对糖脂代谢及睾丸功能的影响.方法 雄性Akt2+/+及Akt2-/-小鼠各15只,行口服糖耐量(OGTT)实验(2 mg/kg),予动力学实验,将纯合子和野生型小鼠分别随机分为2组,空白组和刺激组,刺激组予人绒毛膜促性腺激素(hCG)刺激4 h,空白组予等体积的生理盐水刺激4 h,检测各组小鼠体重、体内脂肪重量、血脂、空腹胰岛素及生殖激素水平.结果 Akt2-/-小鼠同Akt2+/+小鼠相比,餐后随机血糖、0 h、1 h血糖均显著升高(P<0.05);睾丸重量显著增加(P<0.01).性激素检测发现Akt2-/-小鼠血清雄烯二酮(A2)(P<0.01)和睾酮(T)(P<0.05)显著升高;hCG刺激后,Akt2-/-与Akt2+/+小鼠的17-羟孕酮(17-OHP)、A2和T均显著升高,但Akt2+/+小鼠的T升高更明显.结论 Akt2基因不仅影响糖代谢,同时影响睾丸功能,说明胰岛素调节糖代谢的关键信号分子可能对睾丸生殖功能同样具有重要的调节作用.hCG刺激后,同Akt2+/+小鼠相比,Akt2-/-小鼠A2和T升高的幅度较小,说明Akt2基因缺失使雄激素合成亢进,但降低了睾丸对hCG的敏感性.%Objective: To study the glycolipid metabolism profile and testicular functions in Akt2 knockout (Akt2 -/-) male mice and wild-type mice (Akt2+/+).Methods: Fifteen Akt2-/- adult male mice and 15 Akt2+/+ adult male mice were used for the experiment.Each mouse was caged individually under controlled environmental conditions.The oral glucose tolerance test (OGTT) and hCG stimulation test were made.The serum levels of insulin, low density lipoprotein-cholesterol (LDL-C), triglyceride (TG ), total cholesterol (CHO), 17-alphahydroxyprogesterone (17-OHP), androstendione (A2) and testosterone (T) were measured.The body weight, testis weight, epididymal and inguinal fat pad weight were all recorded.The histomorphology of testes were observed under light microscope.Results: Akt2-/- mice had a significant increase in fasting or postprandial blood glucose levels compared with Akt2+/+ mice (P＜0.05).The levels of blood glucose at 0 and 1 hour during OGTT were significantly higher in Akt2-/- mice than in Akt2+/+ mice (P＜0.05).The testis weight of Akt2 -/- mice was significantly increased (P＜O.05).Akt2-/- mice showed higher levels of serum T (P＜0.05) and A2 (P＜0.01) than wide type mice.The serum levels of 17-OHP, A2 and T were significantly increased both in Akt2-/- mice and Akt2+/+ mice after hCG stimulation, while the increase in levels of A2 and T was more significant in Akt2+/+mice than in Akt2-/- mice.Conclusions: Male Akt2-/- mouse showed an abnormal profile of glucose metabolism, suggesting a key role of Akt2 in the maintenance of a normal glucose homoeostasis.Male Akt2-/- mouse had a hyperfunction in the synthesis of A2 and T, but a reduced response to the hCG stimulation.