七福饮调控JAK2/STAT3通路改善2型糖尿病认知障碍的效应与机制  

Effect and mechanism of Qifu Yin regulation of JAK2/STAT3 pathway to improve type 2 diabetic cognitive impairment

作　　者：刘玲 张静文 张瑞华 史磊磊 王晨 韩朝军 史永恒[1] 王斌[1] 刘继平[1] LIU Ling;ZHANG Jing-wen;ZHANG Rui-hua;SHI Lei-lei;WANG Chen;HAN Chao-jun;SHI Yong-heng;WANG Bin;LIU Ji-ping(Shaanxi University of Chinese Medicine,Xianyang Shaanxi 712000,China)

机构地区：[1]陕西中医药大学,陕西咸阳712000

出　　处：《中国药理学通报》2022年第7期1093-1098,共6页Chinese Pharmacological Bulletin

基　　金：陕西省重点研发计划项目(No 2021SF-072);陕西中医药大学学科创新团队(No 2019-YL13)。

摘　　要：目的研究七福饮(QFY)对2型糖尿病认知障碍大鼠JAK2/STAT3通路的调控作用。方法采用小剂量STZ联合高脂高糖饲料喂养的方法造模,成功后分成模型组、QFY低、高剂量组、二甲双胍组。干预4周后,检测空腹血糖;Morris水迷宫检测大鼠空间学习记忆能力;尼氏染色和免疫荧光染色检测大脑损伤程度以及小胶质细胞标志物Iba-1的表达;ELISA检测TNF-α、IL-6、IL-10和BDNF的表达;Western blot检测JAK2/STAT3通路的表达。结果与正常组相比,模型组血糖升高明显,空间学习记忆能力下降,海马神经元损伤严重,小胶质细胞活化增多,TNF-α、IL-6、p-JAK2/JAK2和P-STAT3/STAT3水平明显升高,IL-10和BDNF含量明显下降;与模型组相比,QFY能有效降低FBG,抑制FBG持续上升,提高学习记忆能力,改善海马神经元损伤,减少活化结论QFY具有改善2型糖尿病认知障碍的作用,其机制可能与抑制血糖上升,调控JAK2/STAT3通路抑制小胶质细胞活化有关。Objective To explore the regulatory effect of Qifu Yin(QFY)on JAK2/STAT3 pathway in rats with type 2 diabetic cognitive impairment.Methods A small dose of STZ combined with high-fat and high-sugar feed was used to build the model.After success,they were divided into model group,QFY low-dose,high-dose group,and metformin group.After four weeks of intervention,fasting blood glucose(FBG)was measured;Morris water maze was used to detect spatial learning and memory ability in rats;Nissl staining and immunofluorescence staining were respectively used to detect the degree of brain injury and the expression of Iba-1,a marker of microglia.ELISA was used to detect the expression of TNF-α,IL6,IL10 and BDNF.Western blot was employed to detect the expression of JAK2/STAT3 pathway.Results Compared with the control group,the model group showed significant increase in blood glucose,decreased spatial learning and memory capacity,severely damaged hippocampal neurons,increased activated microglia,significantly higher levels of TNF-α,IL6,p-JAK2/JAK2 and p-STAT3/STAT3,and significantly lower levels of IL10 and BDNF.Compared with the model group,QFY group effectively reduced FBG,inhibited the continuous rise of FBG,improved learning and memory ability,improved hippocampal neuronal damage,reduced activated microglia,reduced TNF-α,IL6,p-JAK2/JAK2 and p-STAT3/STAT3 levels,and increased IL10 and BDNF levels.Conclusion QFY has been shown to improve type 2 diabetic cognitive impairment,and the mechanism may be related to the inhibition of blood glucose rise and regulation of the JAK2/STAT3 pathway,thereby inhibiting microglia activation.

关 键 词：七福饮 2型糖尿病认知障碍 小胶质细胞 炎症因子 JAK2/STAT3通路 

分 类 号：R-332[医药卫生] R285.5R322.81R392.12R587.1R741