大补元煎通过调控PPARγ/NF-κB信号通路改善轻度认知障碍小鼠学习记忆能力  

Dabuyuan Jian improves learning and memory ability of mild cognitive impairment mice via modulating PPARγ/NF-κB signaling pathway

作　　者：李玮怡 田梦杰 江露 张宗星 刘道忠 包卓玛 王政喻 袁林 LI Weiyi;TIAN Mengjie;JIANG Lu;ZHANG Zongxing;LIU Daozhong;BAO Zhuoma;WANG Zhengyu;YUAN Lin(Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases,Hubei Minzu University,Enshi 445000,China;Health Science Center,Hubei Minzu University,Enshi 445000,China;Qingdao Hospital of Chinese Medicine,Qingdao 266000,China)

机构地区：[1]湖北民族大学风湿性疾病发生与干预湖北省重点实验室,湖北恩施445000 [2]湖北民族大学医学部,湖北恩施445000 [3]青岛市中医医院,山东青岛266000

出　　处：《中国病理生理杂志》2025年第2期287-293,共7页Chinese Journal of Pathophysiology

基　　金：湖北民族大学研究生教育创新项目(No.MYK2023066)。

摘　　要：目的:研究大补元煎(DBYJ)对轻度认知障碍(MCI)小鼠过氧化物酶体增殖物激活受体γ(PPARγ)/核因子κB(NF-κB)信号通路及相关炎症蛋白的调节作用,探讨其改善MCI小鼠学习和记忆能力的作用机制。方法:将40只C57BL/6雄性小鼠随机分为阴性对照(NC)组、D-半乳糖(D-Gal)组、D-Gal+GW9662(PPARγ抑制剂)组、DGal+DBYJ组和D-Gal+GW9662+DBYJ组,每组8只。NC组小鼠颈背部皮下注射0.9%生理盐水8周,其余4组小鼠颈背部皮下注射D-Gal(100 mg·kg^(-1)·d^(-1))8周来建立MCI模型。第5~8周,D-Gal+GW9662组和D-Gal+DBYJ+GW9662组小鼠腹腔注射GW9662(1 mg·kg^(-1)·d^(-1))。从第5周起,D-Gal+DBYJ组和D-Gal+DBYJ+GW9662组小鼠灌胃DBYJ水煎液(13.2 g/kg),其余3组灌胃等体积纯水,共4周。采用Morris水迷宫(包括定位航线实验和空间探测实验)评估各组小鼠的学习记忆能力;HE染色观察各组小鼠海马结构的完整性;Nissl染色观察各组小鼠海马神经元的损伤情况;Western blot实验检测各组小鼠海马中白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)、PPARγ、P65和磷酸化P65(p-P65)的蛋白水平。结果:与NC组比较,D-Gal+D-Gal组和D-Gal+GW9662组小鼠逃避潜伏期延长,60 s内穿越平台次数和停留在目标象限时间减少(P<0.01);CA3区神经元数量减少(P<0.01),锥体细胞排列紊乱,细胞固缩;TNF-α、IL-1β和p-P65蛋白水平升高,PPARγ水平降低(P<0.05)。与D-Gal组相比,D-Gal+DBYJ组小鼠逃避潜伏期缩短,穿越平台次数和目标象限时间则有所增加(P<0.01);CA3区神经元数量增加(P<0.01),锥体细胞排列整齐,细胞结构完整;TNF-α、IL-1β和p-P65蛋白水平降低,PPARγ水平升高(P<0.05)。与D-Gal+GW9662组相比,D-Gal+DBYJ+GW9662组小鼠逃避潜伏期缩短,目标象限时间和穿越平台次数增加(P<0.05),但效果较D-Gal+DBYJ组差;CA3区神经元数量增加(P<0.01),锥体细胞排列较整齐,细胞结构较完整,但效果较D-Gal+DBYJ组差;TNF-α、IL-1β和p-P65蛋白水平降AIM:To investigate the potential effect of Dabuyuan Jian(DBYJ)on peroxisome proliferator-activated receptorγ(PPARγ)/nuclear factor-κB(NF-κB)signaling pathway and related inflammatory proteins in mice with mild cognitive impairment(MCI),and to explore the mechanism of DBYJ in improving the learning and memory ability of MCI mice.METHODS:Forty C57BL/6 male mice were randomly divided into 5 groups,including negative control(NC)group,D-galactose(D-Gal)group,D-Gal+DBYJ group,D-Gal+GW9662(PPARγinhibitor)group and D-Gal+GW9662+DBYJ group,with 8 mice each.The mice in NC group were subcutaneously injected with 0.9%saline solution on the back of the neck for 8 weeks,while those in the remaining 4 groups were subcutaneously injected with D-Gal(100 mg·kg^(-1)·d^(-1))on the back of the neck for 8 weeks to establish the MCI model.From week 5 to week 8,the mice in D-Gal+GW9662 and D-Gal+DBYJ+GW9662 groups were intraperitoneally injected with GW9662(1 mg·kg^(-1)·d^(-1)).From week 5,the mice in D-Gal+DBYJ and D-Gal+DBYJ+GW9662 groups were treated with DBYJ(13.2 g/kg)by gavage,while those in the re-maining 3 groups were administered an equal volume of purified water for 4 weeks.The Morris water maze(including posi-tioning navigation experiment and space exploration experiment)was used to assess the learning and memory ability of the mice.The structural integrity of the hippocampus of the mice was assessed by hematoxylin-eosin(HE)staining.Nissl staining was used to evaluate damage to hippocampal neurons in mice,and Western blot was applied to detect the protein levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),PPARγ,P65 and phosphorylated P65(p-P65)in the hippocampus of the mice.RESULTS:Compared with NC group,the escape latency of the mice in D-Gal+D-Gal and D-Gal+GW9662 groups significantly increased(P<0.01),while the number of platform crossing and the duration of staying in the target quadrant within 60 s significantly decreased(P<0.01).The number of neurons in the CA3 region remarkably decreased(P<0.0

关 键 词：大补元煎 轻度认知障碍 学习 记忆 PPARγ/NF-κB信号通路 

分 类 号：R285.5[医药卫生—中药学] R741[医药卫生—中医学] R363.2