益糖康调控AMPK/mTOR信号通路激活自噬抑制NLRP3炎症小体改善糖尿病认知功能障碍的机制研究  

Study on the mechanism of Yitangkang regulating AMPK/mTOR signaling pathway,activation of autophagy and inhibition of NLRP3 inflammasome on diabetic cognitive dysfunction

作　　者：苏嘉楠 敖玉涵 安继仁 孙贵炎 杨宇峰[1] 石岩[1] SU Jianan;AO Yuhan;AN Jiren;SUN Guiyan;YANG Yufeng;SHI Yan(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China)

机构地区：[1]辽宁中医药大学,沈阳110847

出　　处：《中华中医药杂志》2025年第3期1074-1080,共7页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：基金资助:国家中医药领军人才支持计划-岐黄学者(No.[2018]12);辽宁省“兴辽英才计划”青年拔尖人才资助项目(No.XLYC1807145);辽宁省人社厅百千万人才资助项目(No.20200512)。

摘　　要：目的:从体内外两方面探讨益糖康通过激活AMPK/mTOR信号通路介导的自噬-NLRP3炎症小体通路治疗糖尿病认知功能障碍(DCI)的机制。方法:分别采用SPF级9周龄雄性C57BL/6J背景db/db小鼠、高糖诱导HT22神经元细胞构建体内、外模型并设立相应分组。体内实验方面,记录糖代谢等相关指标并进行Morris水迷宫实验;同时,进行HE染色和尼氏染色。体外实验方面,采用CCK8法检测细胞活力。体内、外实验均采用Western Blot检测AMPK/mTOR、自噬及炎症小体相关蛋白的表达情况。结果:体内实验证实,与db/db组比较,YTK组小鼠糖代谢、认知功能、神经元损伤情况得到缓解;AMPK/mTOR、自噬及炎症小体等相关蛋白表达显著改善。体外实验证实,YTK组神经细胞在形态、生长和排列分布呈不同程度改善。体外Western Blot结果与体内实验趋势基本相同,进一步验证了体内实验的结果。同时,体外实验应用相应抑制剂对AMPK/mTOR信号通路、自噬及炎症小体三者的上下游关系进行了验证。结论:益糖康能够调控AMPK/mTOR表达进而激活自噬抑制NLRP3炎症小体活化治疗DCI。Objective:To explore the mechanism of Yitangkang in treating diabetes cognitive dysfunction(DCI)by activating the autophagy-NLRP3 infammasome mediated by AMPK/mTOR signaling pathway in vivo and in vitro.Method:SPF grade 9-week-old male C57BL/6J background db/db mice and HT22 neurons induced by high glucose were used to construct in vitro and in vivo models respectively,and corresponding groups were established.In vivo experiments,glucose metabolism related indexes were recorded and Morris water maze experiment was carried out.Simultaneously,HE staining and Nissl staining were performed.In vitro experiment,CCK8 method was used to detect cell viability.Western Blot was used to detect the expression of AMPK/mTOR,autophagy and NLRP3 inflammasome related proteins in vivo and in vitro.Results:In vivo experiments confirmed that compared with db/db group,the glucose metabolism,cognitive function and neuronal damage in YTK group were alleviated.The expression of AMPK/mTOR,autophagy and NLRP3 inflammasome was significantly improved.In vitro experiments confirmed that the morphology,growth,arrangement and distribution of nerve cells in YTK group were improved to varying degrees.The results of Western Blot in vitro were basically the same as those in vivo,which further verified the results in vivo.Meanwhile,the upstream and downstream relationships among AMPK/mTOR signaling pathway,autophagy and NLRP3 inflammasome were verified by using corresponding inhibitors in vitro experiments.Conclusion:Yitangkang can regulate AMPK/mTOR expression to activate autophagy,and inhibit the subsequent activation of NLRP3 inflammasome,ultimately treat DCI.

关 键 词：益糖康 AMPK/mTOR信号通路 细胞自噬 NLRP3炎症小体 糖尿病认知功能障碍 

分 类 号：R285.5[医药卫生—中药学]