黄连解毒汤对糖尿病认知功能障碍大鼠海马JNK胰岛素信号通路关键蛋白及其磷酸化的影响及机制研究

Effect of Huanglian Jiedu Decoction on Key Proteins and Phosphorylation of JNK Insulin Signaling Pathway for Hippocampus of Diabetes-induced Cognitive Dysfunction Rats

目的:探讨黄连解毒汤对糖尿病认知功能障碍(CID)大鼠海马JNK胰岛素信号通路关键蛋白及其磷酸化的影响及其机制。方法:健康雄性Wistar大鼠100只,随机分为5组,分别为模型组、罗格列酮组、黄连解毒汤低、中、高剂量组,20只雄性SD大鼠为空白对照组,制备2型糖尿病(T2DM)大鼠模型。观察黄连解毒汤对T2DM大鼠水迷宫行为学的影响,测定并检测大鼠海马组织匀浆SOD、MDA及AchE的含量;Western Blot法检测大鼠海马组织JNK信号传导通路关键蛋白JNK/p-JNK、AKT/p-AKT、IRS-1/p-IRS-1水平。结果:黄连解毒汤的应用可以缩短实验大鼠逃避时间,延长停留时间、游泳路程和逃逸次数;抑制关键蛋白JNK、IRS-1磷酸化,促进AKT磷酸化,进而增强大鼠海马组织SOD活性,降低MDA、AchE水平,增强组织抗氧化能力,减轻了氧化应激水平,从而改善思维,提高记忆和学习功能。结论:黄连解毒汤干预CID的作用机制,可能是通过调控JNK、Akt、IRS-1表达,调节SOD、MDA、AchE水平来实现的。

Objective: To explore the effect of Huanglian Jiedu Decoction on the key proteins and phosphorylation of JNK insulin signaling pathway for hippocampus of diabetic cognitive impairment(CID) rats.Methods: 100 healthy male Wistar rats were randomly divided into 5 groups: model group, rosiglitazone group, Huanglian Jiedu decoction low, medium and high dose group, and 20 males SD rats were used as a blank controlled group, and type 2 diabetes(T2 DM) rat model was prepared and treated with corresponding drugs.To observe the effect of Huanglian Jiedu Decoction on the behavior of water maze in T2 DM rats, and measure and detect the contents of SOD,MDA and AchE in hippocampal homogenate of T2 DM rats, using Western Blot method to detect JNK signaling pathway in hippocampus of rats Key proteins JNK/p-JNK,AKT/p-AKT,IRS-1/p-IRS-1 levels.Results: The application of Huanglian Jiedu Decoction can shorten the escape period of DM rats, increase the dwell time, swimming distance and the number of escapes, inhibit the phosphorylation of key proteins JNK and IRS-1,promote the phosphorylation of AKT,enhance the SOD activity of hippocampus and reduce MDA And AchE levels, enhance the tissue’s antioxidant capacity, reduce the level of oxidative stress, improving thinking and learning and memory functions.Conclusion: The mechanism of Huanglian Jiedu Decoction intervention in CID may be achieved by regulating the expression of JNK,Akt and IRS-1 and regulating the levels of SOD,MDA and AchE.