β-烟酰胺单核苷酸通过抗氧化机制调控血糖平衡的研究

Research on the regulation of blood glucose balance by β-nicotinamide mononucleotide through antioxidant mechanisms

中文关键词:  β-NMN  四氧嘧啶  抗氧化  高血糖  血糖平衡

英文关键词:β-nicotinamide mononucleotide  alloxan  antioxidant  hyperglycemia  blood glucose balance

中文摘要:

      目的 探究β-烟酰胺单核苷酸(β-nicotinamide mononucleotide, β-NMN)通过抗氧化机制调控血糖平衡的潜力。方法 通过注射105 mg/kg·BW四氧嘧啶并辅以高脂饲料饲喂建立高血糖模型大鼠, 连续30 d给予SD大鼠不同剂量的β-NMN, 同时设置正常动物对照组, 实验终期对大鼠血清中的血糖、血脂及抗氧化相关因子进行测定。结果 β-NMN对四氧嘧啶模型高血糖大鼠的血糖有一定调控作用, 40 mg/kg剂量组β-NMN可以显著降低该模型大鼠的血糖(P<0.05), 与模型组相比该剂量组0~2 h曲线下面积(area under the curve, AUC)下降6.77% (P<0.05), 血清中血清胆固醇(cholesterol, CHO)与甘油三酯(triglyceride, TG)的含量均显著降低(P<0.05), 各剂量组胰岛抵抗指数均显著降低(P<0.01), 并且各剂量组对正常大鼠的血糖无不良影响。在抗氧化相关因子的测定结果中, 四氧嘧啶引起了大鼠体内氧化应激, 20 mg/kg β-NMN组超氧化物歧化酶(superoxide dismutase, SOD)活性提高5.69% (P<0.01), 4 mg/kg与40 mg/kg组谷胱甘肽(glutathione, GSH)含量增加27.36%、23.79% (P<0.01), 40 mg/kg组蛋白质羰基下降28.20% (P<0.05), 各剂量丙二醛(malondialdehyde, MDA)与晚期糖基化终末产物受体(receptor for advanced glycation end products?, RAGE/AGER)含量均显著低于模型组(P<0.05, P<0.01)。结论 β-NMN可通过烟酰胺腺嘌呤二核苷酸-SIRT1-FoxO3a/PGC-1α轴增强内源性抗氧化能力, 抑制RAGE介导的二次氧化损伤, 进而维持血糖平衡, 可为未来有关于功能性产品的研发应用提供理论依据。

英文摘要:

      Objective To explore the potential of β-nicotinamide mononucleotide (β-NMN) in regulating blood glucose balance through antioxidant mechanisms. Methods A high glucose model rat was established by injecting 105 mg/kg·BW alloxan and feeding it with high-fat diet. SD rats were given different doses of β-NMN for 30 consecutive days. Meanwhile, a normal animal control group was set up. At the end of the experiment, the blood glucose, blood lipids and antioxidant-related factors in the rat serum were measured. Results β-NMN had a certain regulatory effect on the blood glucose of alloxan model high-glucose rats. The 40 mg/kg dose group of β-NMN could significantly reduce the blood glucose of the model rats (P<0.05), and compared with the model group, the area under the curve (AUC) of the 0–2 h curve of this dose group decreased by 6.77% (P<0.05). The contents of serum cholesterol (CHO) and triglyceride (TG) in this dose group were significantly reduced (P<0.05). The insulin resistance index of each dose group was significantly reduced (P<0.01), and there was no adverse effect on the blood glucose of normal rats. In the determination results of antioxidant-related factors, alloxan caused oxidative stress in the rats, and the activity of superoxide dismutase (SOD) in the 20 mg/kg β-NMN group increased by 5.69% (P<0.01), the content of glutathione (GSH) in the 4 mg/kg and 40 mg/kg groups increased by 27.36% and 23.79% (P<0.01), the protein carbonyl content in the 40 mg/kg group decreased by 28.20% (P<0.05), and the content of malondialdehyde (MDA) and receptor for advanced glycation end products (RAGE/AGER) in each dose group were significantly lower than those of the model group (P<0.05, P<0.01). Conclusion β-NMN can enhance the endogenous antioxidant capacity through the nicotinamide adenine dinucleotide-SIRT1-FoxO3a/PGC-1α axis, inhibit secondary oxidative damage mediated by RAGE, and thereby maintain blood glucose balance. This provides a theoretical basis for the future research and application of functional products.