上海交通大学学报（医学版）

上海交通大学学报(医学版) ›› 2022, Vol. 42 ›› Issue (2): 158-165.doi: 10.3969/j.issn.1674-8115.2022.02.004

• 论著 · 基础研究 • 上一篇    

烟酰胺单核苷酸对衰老小鼠代谢的干预作用

党国栋1(), 洪新宇2(), 蔡美琴1()   

  1. 1.上海交通大学公共卫生学院，上海 200025
    2.上海市疾病预防控制中心，上海 200051
  • 收稿日期:2021-10-08 出版日期:2022-02-28 发布日期:2022-03-17
  • 通讯作者: 洪新宇,蔡美琴 E-mail:dang_guodong@126.com;hongxinyu@scdc.sh.cn;caimeiqin@sjtu.edu.cn
  • 作者简介:党国栋（1997—），男，硕士生；电子信箱：dang_guodong@126.com。

Interventional effects of nicotinamide mononucleotide on metabolism in aging mice

Guodong DANG1(), Xinyu HONG2(), Meiqin CAI1()   

  1. 1.School of Public Health, Shanghai Jiao Tong University, Shanghai 200025, China
    2.Shanghai Center for Disease Control and Prevention, Shanghai 200051, China
  • Received:2021-10-08 Online:2022-02-28 Published:2022-03-17
  • Contact: Xinyu HONG,Meiqin CAI E-mail:dang_guodong@126.com;hongxinyu@scdc.sh.cn;caimeiqin@sjtu.edu.cn

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摘要：

目的·研究烟酰胺单核苷酸（nicotinamide mononucleotide，NMN）对衰老小鼠代谢的影响。方法·采用随机数字表将70只C57BL/6N雄性小鼠随机分为5组，分别为对照组、早衰模型组、干预Ⅰ组、衰老模型组和干预Ⅱ组，每组14只。除对照组外，其余4组小鼠颈背部皮下注射D-半乳糖（D-galactose，D-gal）（150 mg/kg），建立小鼠衰老模型；干预Ⅰ组和干预Ⅱ组同时灌胃给予NMN（300 mg/kg），其余各组给予等量的蒸馏水，均每日1次，早衰模型组和干预Ⅰ组持续6周，衰老模型组和干预Ⅱ组持续12周；对照组给予等量的生理盐水和蒸馏水，每日1次，持续6周。造模6周后检测对照组、早衰模型组、干预Ⅰ组小鼠呼吸代谢量、活动量、能量消耗等能量代谢监测指标，计算胸腺、脾脏、肝脏、肾脏的脏器指数，检测糖耐量和胰岛素敏感性以及血清和肝脏中的超氧化物歧化酶（superoxide dismutase，SOD）活性、谷胱甘肽过氧化物酶（glutathione peroxidase，GSH-Px）活性、丙二醛（malondialdehyde，MDA）含量。造模12周后对衰老模型组和干预Ⅱ组进行上述指标的检测。结果·与对照组比较，早衰模型组和衰老模型组小鼠胸腺指数（P=0.035，P=0.000）和肾脏指数（P=0.009，P=0.002）降低，夜晚的O2消耗量（P=0.018，P=0.000）、CO2呼出量（P=0.044，P=0.003）、活动量（均P=0.000）和能量消耗（P=0.010，P=0.001）显著下降，胰岛素敏感性降低（P=0.012，P=0.011），血清SOD（P=0.002，P=0.001）、GSH-Px（P=0.001，P=0.011）活性显著下降，MDA含量显著升高（均P=0.000）。能量代谢监测指标、胸腺和肾脏指数以及抗氧化指标的下降验证了D-gal衰老模型造模成功。与早衰模型组相比，干预Ⅰ组在呼吸代谢、能量消耗、糖耐量和胰岛素敏感性等指标方面差异无统计学意义（均P>0.05），活动量（P=0.022）和血清SOD（P=0.026）、GSH-Px（P=0.006）活性显著升高，MDA含量显著降低（P=0.011）。与衰老模型组相比，干预Ⅱ组夜晚的O2消耗量（P=0.045）、CO2呼出量（P=0.030）、活动量（P=0.049）和能量消耗（P=0.043）显著增加，糖耐量受损得到改善（P=0.030），胰岛素敏感性提高（P=0.010），血清SOD活性显著升高（P=0.046），血清及肝组织中的MDA含量显著降低（P=0.000），2组间血清及肝组织中的GSH-Px活性差异无统计学意义（均P>0.05）。结论·NMN能一定程度改善衰老小鼠的代谢水平，其作用机制很可能与提高机体的抗氧化能力有关。

关键词: 烟酰胺单核苷酸, 衰老, 能量代谢, 糖耐量, 胰岛素敏感性, 抗氧化

Abstract:

Objective·To investigate the effects of nicotinamide mononucleotide (NMN) on metabolism in aging mice.

Methods·Seventy C57BL/6N male mice were randomly divided into 5 groups by using a table of random numbers. They were the control group, the premature aging model group, the aging model group, the intervention group Ⅰand the intervention group Ⅱ. Each group contained 14 mice. Except the control group, D-galactose (D-gal) (150 mg/kg) was subcutaneously injected into the napes of mice in the other 4 groups to establish the aging model of mice. NMN (300 mg/kg) was given to the intervention group Ⅰ and the intervention group Ⅱ by intragastric administration at the same time, and the other groups were given the same amount of distilled water, once a day, for 6 weeks in the premature aging model group and the intervention group Ⅰ, and for 12 weeks in the aging model group and the intervention group Ⅱ. The control group was given the same amount of normal saline and distilled water, once a day, for 6 weeks. Six weeks after modeling, the energy metabolism levels of the mice in the control group, the premature aging model group and the intervention group Ⅰ were detected, including respiratory metabolism, activity level and energy consumption. The organ indexes of thymus, spleen, liver and kidney were calculated. The glucose tolerance and insulin sensitivity were measured. In addition, the content of superoxide dismutase (SOD) and the activities of glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in the serum and liver tissue were detected. Twelve weeks after modeling, the above indexes were detected in the aging model group and the intervention group Ⅱ.

Results·Compared with the control group, the thymus index (P=0.035, P=0.000) and renal index (P=0.009, P=0.002) of the model groups were significantly decreased. The O2 consumption (P=0.018, P=0.000), CO2 exhalation (P=0.044, P=0.003), energy consumption (P=0.010, P=0.001) and activity ability (both P=0.000) of the premature aging model group and the aging model group were significantly decreased at night. The insulin sensitivity was significantly reduced (P=0.012, P=0.011). The activities of SOD (P=0.002, P=0.001) and GSH-Px (P=0.001, P=0.011) in serum were significantly decreased and the content of MDA in serum was significantly increased (both P=0.000). The decline of energy metabolism levels, thymus and kidney indexes and antioxidant index verified the success of D-gal aging model. Compared with the premature aging model group, the intervention group Ⅰ had no significant difference in respiratory metabolism, energy consumption, glucose tolerance, insulin sensitivity and other indicators (all P>0.05). But in the intervention group Ⅰ, the activity ability was significantly improved (P=0.022), the activities of SOD (P=0.026) and GSH-Px (P=0.006) in serum were significantly increased, and the MDA content in serum was significantly decreased (P=0.011). Compared with the aging model group, the O2 consumption (P=0.045), CO2 exhalation (P=0.030), activity ability (P=0.049) and energy consumption (P=0.043) in the intervention group Ⅱ were significantly increased at night. Compared with the aging model group, the impaired glucose tolerance was improved (P=0.030), the insulin sensitivity was increased (P=0.010)in the intervention group Ⅱ, the activity of SOD in serum was significantly increased (P=0.046), and the MDA content in serum and liver tissue was significantly decreased (P=0.000). There was no significant difference in the activity of GSH-Px in serum and liver tissue between the two groups (P>0.05).

Conclusion·NMN can improve the metabolic level of aging mice to a certain extent, and its mechanism may be related to improving the antioxidant capacity of the body.

Key words: nicotinamide nucleotide (NMN), aging, energy metabolism, glucose tolerance, insulin sensitivity, antioxidation

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