孔圣枕中丹对糖尿病认知功能障碍小鼠海马组织RAS/RAF/MEK信号通路的影响OA
Impact of Kongsheng Zhenzhong Dan on RAS/RAF/MEK signaling path-way in hippocampal tissue of diabetic cognitive dysfunction mice
目的:探究孔圣枕中丹对糖尿病认知功能障碍(DCD)小鼠海马组织大鼠肉瘤(RAS)/快速加速纤维肉瘤(RAF)/丝裂原活化蛋白激酶激酶(MEK)信号通路的影响.方法:选取10 只 db/m 小鼠作为空白组,30 只 db/db小鼠随机平均分为模型组、二甲双胍组和孔圣枕中丹组.空白组和模型组灌胃 10 mL/(kg·d)生理盐水,二甲双胍组灌胃200 mg/(kg·d)二甲双胍水溶液,孔圣枕中丹组灌胃33.8 g/(kg·d)孔圣枕中丹水溶液,每日灌胃1 次,连续12 周.检测空腹血糖之后采用 Morris 水迷宫实验评估小鼠学习记忆能力;取海马组织,HE 和尼氏染色行病理学观察,透射电镜下观察神经元超微结构,Western blot 法检测 RAS、RAF 蛋白表达及 MEK 磷酸化水平,RT-qPCR法检测 RAS、RAF 及 MEK mRNA 的表达.结果:与模型组比较,二甲双胍组和孔圣枕中丹组空腹血糖下降,逃避潜伏期缩短,穿越平台次数和目标象限停留时间增加(P<0.001);海马神经元形态有所改善,尼氏小体数量增加,线粒体结构相对完整,线粒体嵴清晰;RAS、RAF 蛋白表达水平及 MEK 磷酸化水平降低(P<0.05),RAS、RAF mRNA表达水平降低(P<0.05).结论:孔圣枕中丹可能通过抑制 RAS/RAF/MEK 信号通路,改善 DCD 小鼠的认知功能障碍.
Aim:To investigate the effects of Kongsheng Zhenzhong Dan(KSZZD)on RAS/RAF/MEK signal pathway of diabetic cognitive dysfunction mice.Methods:Ten db/m mice were selected as the control group,while 30 db/db mice were randomly divided into the model group,the metformin group,and the KSZZD group.The control group and model group received oral administration of 10 mL/(kg·day)of normal saline solution,the metformin group received 200 mg/(kg·day)of metformin aqueous solution,and the KSZZD group received 33.8 g/(kg·day)of KSZZD solution,once daily for 12 weeks.The fasting blood glucose was determined.Subsequently,Morris water maze test was performed to assess the learn-ing and memory abilities;hippocampal tissues were examined via HE and Nissl staining for pathological analysis,neuronal ultrastructure was observed under transmission electron microscopy,RAS and RAF protein expression level as well as MEK phosphorylation level were determined by Western blot,and RAS,RAF,and MEK mRNA expression levels were measured by RT-qPCR.Results:Compared with the model group,both the metformin group and the KSZZD group exhibited reduced fasting blood glucose levels,shortened escape latency,increased number of platform crossings,and prolonged dwell time in target quadrants(P<0.001);the hippocampal neuronal morphology was improved with increased Nissl bodies,relatively in-tact mitochondrial structures,and clear mitochondrial cristae;additionally,the protein expression levels of RAS and RAF,and MEK phosphorylation levels,as well as the mRNA expression levels of RAS and RAF were decreased(P<0.05).Conclu-sion:KSZZD may ameliorate diabetic cognitive dysfunction by inhibiting the RAS/RAF/MEK signaling pathway.
左铭钰;马倩倩;符竣轲;李鑫;闫国立
河南中医药大学中医(仲景)学院 郑州 450046河南中医药大学中医(仲景)学院 郑州 450046河南中医药大学中医(仲景)学院 郑州 450046河南中医药大学中医(仲景)学院 郑州 450046河南中医药大学医学院 郑州 450046
医药卫生
糖尿病认知功能障碍孔圣枕中丹RAS/RAF/MEK信号通路小鼠
diabetic cognitive dysfunctionKongsheng Zhenzhong DanRAS/RAF/MEK signal pathwaymice
《郑州大学学报(医学版)》 2026 (4)
5-10,6
国家自然科学基金(82104748)河南省科技研发计划联合基金项目(252301420100)河南省科技攻关计划项目(242102311282)
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