摘要
目的:探讨地菍总黄酮对2型糖尿病(T2DM)小鼠认知障碍的改善作用及潜在机制。方法:高脂饮食联合链脲佐菌素(STZ)诱导雄性C57BL/6J小鼠构建T2DM模型,将空腹血糖(FBG)≥16.7 mmol/L的小鼠按随机数字表法分为T2DM模型组、二甲双胍组(0.5 g/kg)、多奈哌齐组(0.001 g/kg)、地菍总黄酮量高剂量、中剂量、低剂量组(1.2、0.8、0.6 g/kg),每组12只,给予相对应药物灌胃给药的同时给予高脂饲料喂养8周;另设12只健康小鼠为空白组。记录小鼠体质量、FBG。通过Morris水迷宫评估小鼠空间学习记忆能力;检测脑系数、血清及脑组织中亚铁离子含量、超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)含量;观察海马体形态;检测脑组织中β-淀粉样蛋白(Aβ)、微管相关蛋白Tau、谷胱甘肽过氧化物酶4(GPX4)、核因子E2相关因子2(Nrf2)、前列腺素内过氧化物合成酶2(PTGS2)蛋白的表达。结果:地菍总黄酮能增加T2DM小鼠体质量,降低血糖,改善水迷宫表现,减轻海马体损伤,调节血清及脑组织中亚铁离子、SOD、MDA、GSH含量(P<0.01),降低Aβ、Tau蛋白表达(P<0.01),提高铁死亡关键蛋白PTGS2、Nrf2、GPX4的表达(P<0.01)。结论:地菍总黄酮能降血糖,提高T2DM小鼠的空间学习记忆能力,调节铁代谢,提高抗氧化能力,改善认知障碍,其作用机制可能与调控铁死亡Nrf2/GPX4信号通路有关。
Objective:To investigate the effects and potential mechanisms of total flavonoids from Melastoma dodecandrum Lour.in improving cognitive impairment in type 2 diabetes mellitus(T2DM)mice.Methods:Male C57BL/6J mice were induced to develop T2DM via a high-fat diet combined with streptozotocin(STZ)injection.Mice with fasting blood glucose(FBG)≥16.7 mmol/L were randomly assigned into the following groups(n=12 per group):T2DM model group,metformin group(0.5 g/kg),donepezil group(0.001 g/kg),and high-,medium-,and low-dose total flavonoids of M.dodecandrum groups(1.2,0.8,0.6 g/kg).All treated groups received daily gavage with the respective agents and continued on a high-fat diet for 8 weeks.An additional 12 healthy mice served as the blank control group.Body weight and FBG were recorded.The Morris water maze was used to assess spatial learning and memory.Brain index,and levels of ferrous ion(Fe 2+),superoxide dismutase(SOD),malondialdehyde(MDA),and glutathione(GSH)in serum and brain tissues were measured.Hippocampal morphology was observed histologically.Protein expression levels ofβ-amyloid(Aβ),Tau,glutathione peroxidase 4(GPX4),nuclear factor erythroid 2-related factor 2(Nrf2),and prostaglandin-endoperoxide synthase 2(PTGS2)in brain tissue were also assessed.Results:Total flavonoids of M.dodecandrum increased body weight and reduced blood glucose in T2DM mice,improved performance in the water maze,alleviated hippocampal damage,and regulated Fe 2+,SOD,MDA,and GSH levels in both serum and brain tissues(P<0.01).It significantly reduced the expression of Aβand Tau proteins(P<0.01),while increasing the expression of ferroptosis-related proteins PTGS2,Nrf2,and GPX4(P<0.01).Conclusion:Total flavonoids from M.dodecandrum lower blood glucose,enhance spatial learning and memory in T2DM mice,regulate iron metabolism,boost antioxidant capacity,and alleviate cognitive impairment.These effects may be mediated through modulation of the ferroptosis-related Nrf2/GPX4 signaling pathway.
作者
杨秋莉
莫烨云
唐雨菲
李笑笑
林惠旅
李丽
YANG Qiuli;MO Yeyun;TANG Yufei;LI Xiaoxiao;LIN Huilv;LI Li(College of Pharmacy,Guangxi University of Chinese Medicine,Nanning 530200,China;Key Laboratory of TCM Neuro-metabolism and Immunopharmacology of Guangxi Education Department,Nanning 530200,China;Faculty of Chinese Medicine Science,Guangxi University of Chinese Medicine,Nanning 530222,China;Department of Pharmacy,Nanning Maternal&Child Health Hospital,Nanning 530011,China)
出处
《世界中医药》
北大核心
2025年第12期2101-2107,2112,共8页
World Chinese Medicine
基金
国家自然科学基金项目(81960728)
广西高水平中医药重点学科中药药理学(桂中医药科教发[2023]13号)
广西中医药大学校级科研项目(2022MS013)。
