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CJAP ›› 2019, Vol. 35 ›› Issue (5): 433-437.doi: 10.12047/j.cjap.5816.2019.094

• ORIGINAL ARTICLES • Previous Articles     Next Articles

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

CHENG Jun1, LU Meng-meng2,3,4+, ZHANG Yang2,3△, GAO Ling-yun2, CHEN Chao1, JIANG Hui-xin1,LIU ping1, HUANG Xiu-wen1, LIU Yun-lu3,5   

  1. 1. Clinical Class E of 2014;
    2. School of Basic Medical Sciences;
    3. Key Laboratory of Brain Aging and Neurodegenerative Diseases;
    4. Master's Graduate Student , Grade 2016;
    5. Master's Graduate Student, Grade 2017, Fujian Medical University, Fuzhou 350122, China
  • Received:2019-01-23 Online:2019-09-28 Published:2020-01-02

Abstract: 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.

Key words: metformin, D-galactose, aging, oxidative stress, hippocampal neurons

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