二甲双胍可抑制高脂饮食大鼠中与心脏代谢综合征相关的认知缺陷。
Metformin inhibits cardiometabolic syndrome associated cognitive deficits in high fat diet rats.
作者信息
Chellammal Hanish Singh Jayasingh, Hasan Mizaton Hazizul, Kshirsagar Rahul P, Musukula Vamshi Krishna Reddy, Ramachandran Dhani, Diwan Prakash V
机构信息
Department of Pharmacology and Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam, Selangor 42300 Malaysia.
Department of Pharmacology, Yashodeep Institute of Pharmacy, Sangram Nagar, Aurangabad, 431001 India.
出版信息
J Diabetes Metab Disord. 2022 Jul 18;21(2):1415-1426. doi: 10.1007/s40200-022-01074-4. eCollection 2022 Dec.
OBJECTIVES
Glucose intolerance and insulin resistance are hallmarks of metabolic syndrome and lead to Alzheimer's disease (AD). The purpose of this study is to elucidate the neuroprotective effect of metformin through insulin regulation with cardiometabolic and neurotransmitter metabolic enzyme regulation in high-fat, high-sucrose diet and streptozotocin (HFHS-STZ)-induced rats.
METHODS
Male Wistar rats were treated with metformin (180 mg/kg and 360 mg/kg). STZ (35 mg/kg i.p.) injection was performed on the 14th day of 42 days of HFHS diet treatment. Brain neurotransmitter metabolic enzymes (acetylcholinesterase and monoamine oxidase) were determined along with sodium-potassium ATPase (NaK-ATPase). Plasma lipids and homeostasis model assessment of insulin resistance (HOMA-IR) was performed. Mean arterial blood pressure, heart rate and electrocardiogram (QT, QTc and RR intervals) were analysed with PowerLab.
RESULTS
Metformin treatment significantly ( 0.001) reduced the HOMA-IR index and decreased neurotransmitter metabolic enzymes such as AChE and MAO ( 0.01 and 0.05). The lipid profile was significantly ( 0.001) controlled with cardiometabolic functions.
CONCLUSIONS
Our investigation revealed that metformin has a remarkable role in regulating brain insulin, vascular system with monoaminergic metabolic enzymes and enhancing synaptic plasticity. Metformin may be a selective early therapeutic agent in metabolic syndrome associated with cognitive decline.
目的
葡萄糖耐量异常和胰岛素抵抗是代谢综合征的标志，并会导致阿尔茨海默病（AD）。本研究的目的是阐明二甲双胍在高脂、高糖饮食和链脲佐菌素（HFHS-STZ）诱导的大鼠中通过胰岛素调节以及心脏代谢和神经递质代谢酶调节所产生的神经保护作用。
方法
对雄性Wistar大鼠给予二甲双胍（180mg/kg和360mg/kg）治疗。在高脂高糖饮食治疗42天的第14天腹腔注射链脲佐菌素（35mg/kg）。测定脑神经递质代谢酶（乙酰胆碱酯酶和单胺氧化酶）以及钠钾ATP酶（NaK-ATPase）。进行血脂和胰岛素抵抗稳态模型评估（HOMA-IR）。使用PowerLab分析平均动脉血压、心率和心电图（QT、QTc和RR间期）。
结果
二甲双胍治疗显著（<0.001）降低了HOMA-IR指数，并降低了神经递质代谢酶如乙酰胆碱酯酶和单胺氧化酶（<0.01和<0.05）。血脂水平通过心脏代谢功能得到显著（<0.001）控制。
结论
我们的研究表明，二甲双胍在调节脑胰岛素、具有单胺能代谢酶的血管系统以及增强突触可塑性方面具有显著作用。二甲双胍可能是与认知衰退相关的代谢综合征的一种选择性早期治疗药物。
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