二甲双胍对D-半乳糖诱导雄性中年小鼠衰老的干预作用*

目的:探讨二甲双胍(Met)对D-半乳糖(D-gal)诱导雄性中年小鼠衰老的干预作用。方法:50只ICR 9月龄雄性小鼠,在SPF级实验环境饲养,自由摄食与饮水。随机分5组:对照组,模型组,二甲双胍低、中、高剂量(Met 50 mg/kg,Met 100 mg/kg,Met 200 mg/kg)组,每组10只。Met组和模型组小鼠每日颈背部皮下注射D-gal 100 mg/ kg,同时分别给予Met(50、100、200 mg/kg)或等体积NS灌胃。对照组注射和灌胃等体积NS。连续8周给药。检测小鼠一般状态,体重,空腹血糖,血清和肝脏超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量水平;水迷宫实验检测学习记忆能力;HE染色观察小鼠海马组织结构。结果:每日Met 200 mg/kg干预,能减少模型小鼠的体重。Met干预对模型鼠正常空腹血糖无影响。每日Met 50、100、200 mg/kg剂量干预,与模型组相比,均能显著提升模型小鼠血清和肝组织的SOD活性(P＜0.05)、降低血清MDA含量(P＜0.05),改善学习记忆能力测试的大部分指标(P＜0.05),HE染色显示海马齿状回核固缩、深染的神经元明显减少。Met干预在大部分指标上呈剂量-效应依赖关系。结论:每日Met 50～200 mg/kg长期处理,以Met 200 mg/kg为显著,能延缓D-gal 诱导的雄性中年衰老模型小鼠的衰老进程,机制可能与降低小鼠体重与增强机体抗氧化水平有关。

Interventional effects of metformin on senescence induced by D-galactose in middle-aged male mice

Objective: To investigate the effects of metformin (Met) on middle-aged male mice aging induced by D-galactose. Methods: Fifty nine-month-old male ICR mice were fed in SPF experimental environment and fed freely with water. Subsequently, the mice were randomly divided into 5 groups(n=10): control group, model group, metformin low, medium and high dose groups(Met 50 mg/kg, Met 100 mg/kg, Met 200 mg/kg). The mice in different doses of Met group and model group were subcutaneously injected with D-galactose 100 mg/kg at the back of neck to induce senescence every day. At the same time, the mice were respectively treated with Met (50, 100, 200 mg/kg) or NS of equal volume by gavage. The control group was injected and gavage with equal volume NS. All treatments lasted for 8 weeks. During the study, the general condition, body weight, blood glucose,the activities of superoxide dismutase (SOD) and malonic dialdehyde (MDA) in serum and liver tissue of each mouse were tested, learning and memory ability were measured by Mirris water maze test, HE staining was used to observe the pathology of hippocampus in the mice. Results: Met 200 mg/kg per day could reduce body weight (P＜0.05). Met intervention had no effect on normal fasting blood glucose in model rats. Compared with model group, the daily dose of Met 50, 100, 200 mg/kg could significantly increase SOD activity in serum and liver tissues of model mice (P＜0.05) and decrease MDA content in serum of model mice (P＜0.05), and improve most of the indicators of learning and memory ability of Morris water maze test (P＜0.05). HE staining showed that the neurons with nuclear condensation and deep staining were obviously decreased in the dentate gyrus of hippocampus. Met intervention has dose-dependent effects on most indicators. Conclusion: Long-term treatment of Met can delay the aging process of middle-aged male mice induced by D-galactose, which may be related to reducing the weight of mice and enhancing the body's antioxidant level.