摘要
目的 探讨黄连解毒汤对淀粉样前体蛋白(APP)/早老素1(PS1)双转基因小鼠空间记忆能力及神经元损伤的影响及其机制。方法 30只3月龄APP/PS1双转基因小鼠按照随机数字表法分为模型组、黄连解毒汤组和多奈哌齐组,另外10只同窝野生型C57BL/6J小鼠作为正常对照组,黄连解毒汤组小鼠灌胃黄连解毒汤650 mg/kg,多奈哌齐组小鼠灌胃0.92 mg/kg多奈哌齐,每日1次,连续90 d。Morris水迷宫实验检测小鼠空间记忆能力,ELISA法检测海马组织中APP和β淀粉样蛋白(Aβ)表达水平,HE染色观察海马组织中神经元数量和结构qRT-PCR法检测脑组织中葡萄糖转运蛋白1(GLUT1)、GLUT3、磷脂酰肌醇3-激酶(PI3K)和蛋白激酶(AKT)mRNA表达量,蛋白印迹法检测脑组织中GLUT1、GLUT3、p-PI3K和p-AKT蛋白表达量。结果 与正常对照组比较,模型组小鼠逃避潜伏期延长,平台位置停留时间和穿越次数均减少,APP、Aβ_(1-42)和Aβ_(1-40)表达水平升高,海马组织中神经元排列紊乱,数量减少,PI3K和AKT mRNA表达量升高,GLUT1和GLUT3 mRNA表达量下降,p-PI3K、p-AKT、GLUT1和GLUT3蛋白表达量降低(P<0.05);与模型组比较,黄连解毒汤组和多奈哌齐组小鼠逃避潜伏期缩短,平台位置停留时间和穿越平台次数均增加,APP、Aβ_(1-42)和Aβ_(1-40)表达水平下降,海马组织中神经元排列相对整齐,数量增多,PI3K和AKT mRNA表达量降低,GLUT1和GLUT3 mRNA表达量升高,p-PI3K、p-AKT、GLUT1和GLUT3蛋白表达量均升高(P<0.05)。结论 黄连解毒汤可提高APP/PS1双转基因小鼠空间记忆能力,减轻神经元损伤,其可能是通过激活PI3K/AKT信号通路,同时促进GLUT1和GLUT3表达发挥作用。
Objective To investigate the effects of Huanglian Jiedu Decoction on the spatial memory ability and neuronal injury of APP/PS1 double-transgenic mice and its mechanisms.Methods Thirty 3-month old APP/PS1 double-transgenic mice were divided into a model group,a Huanglian Jiedu Decoction group and a donepezil group according to the random number table method,and 10 wild-type C57/BL6J mice in the same litter were used as a normal control group.The mice in the Huanglian Jiedu Decoction group were given Huanglian Jiedu Decoction 650 mg/kg by gavage,while the mice in the donepezil group were given 0.92 mg/kg donepezil by gavage,once a day for 90 days.Morris water maze test was used to detect the spatial memory ability of mice,and the expression levels of APP and amyloid beta(Aβ)in hippocampus were detected by ELISA.The mRNA expression levels of glucose transporter 1(GLUT1),GLUT3,phosphatidylinositol 3-kinase(PI3K)and protein kinase(AKT)were detected by qRT-PCR,and the protein expression levels of GLUT1,GLUT3,p-PI3K and p-AKT were detected by Western blot.Results Compared with the normal control group,the escape latency of mice in the model group was prolonged,the residence time of platform position and crossing times were reduced,the expression levels of APP,Aβ_(1-42)and Aβ_(1-40),the mRNA expression levels of PI3K and AKT were increased,and the mRNA expression of GLUT1 and GLUT3,the protein expression levels of P-PI3K,P-AKT,GLUT1 and GLUT3 were decreased(P<0.05).Compared with the model group,the escape latency of mice in the Huanglian Jiedu Decoction group and the donepezil group was shortened,the residence time of platform location and the number of crossing platforms were increased,the expression levels of APP,AβBi-42 and Aβi-40,the mRNA expression levels of PI3K and AKT were decreased,and the mRNA expression levels of GLUT1 and GLUT3,the protein expression levels of P-PI3K,P-AKT,GLUT1 and GLUT3 were all increased(P<0.05).Conclusion Huanglian Jiedu Decoction can improve the spatial memory ability of APP/PS1 double-transgenic mice and reduce the neuronal damage,which may play a role by activating the PI3K/AKT signaling pathway and promoting the expression of GLUT1 and GLUT3.
作者
何瑛琨
李士杰
常玉娟
蔡春江
张军娜
HE Yingkun;LI Shijie;CHANG Yujuan;CAI Chunjiang;ZHANG Junna(Department of Traditional Chinese Medicine,Hebei General Hospital,Shijiazhuang 050000,China;Department of Myasthenia Gravis,Yiling Hospital,Shijiazhuang 050000,China;Department of Gastroenterology/Department of Gastrointestinal Diseases,Traditional Chinese Medicine Hospital of Shiiazhuang City,Shijazhuang 050000,China)
出处
《吉林中医药》
2025年第8期951-955,共5页
Jilin Journal of Chinese Medicine
基金
河北省中医药管理局科研计划项目(2020207)。
