杞参益智方改善D-半乳糖注射亚急性衰老模型小鼠学习与记忆能力的效应评价研究  

Efficacy Evaluation of Qishen Yizhi Formula in Improving the Learning and Memory Ability of D-Galactose Induced Subacute Aging Mice

作　　者：陈杨 朱梓强 陆韫青 郑嘉妮 曹程 仝佳祥 李璇 郭盛[1] 康宏杰 段金廒[1] 朱悦[1] CHEN Yang;ZHU Ziqiang;LU Yunqing;ZHENG Jiani;CAO Cheng;TONG Jiaxiang;LI Xuan;GUO Sheng;KANG Hongjie;DUAN Jinao;ZHU Yue(School of Pharmacy,Jiangsu Province Key Laboratory of Prescription Research,Jiangsu Province Key Laboratory of Prescription High Technology Research,National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine,Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization,Nanjing University of Chinese Medicine,Nanjing 210023,China;Ningxia Innovation Center of Goji R&D,Yinchuan 750000,China)

机构地区：[1]南京中医药大学药学院,江苏省方剂研究重点实验室/江苏省方剂高技术研究重点实验室/中药资源产业化与方剂创新药物国家地方联合工程研究中心/江苏省中药资源产业化过程协同创新中心,江苏南京210023 [2]宁夏枸杞创新中心,宁夏银川750000

出　　处：《南京中医药大学学报》2024年第2期145-152,共8页Journal of Nanjing University of Traditional Chinese Medicine

基　　金：国家重点研发计划项目(2022YFE0201700);宁夏重点研发计划重点项目(2021BEF02009,2022BFH02008);宁夏科技基础条件建设项目(2021DPC05005);江苏省研究生科研与实践创新计划(SJCX22_0796)。

摘　　要：目的评价杞参益智方对D-半乳糖注射亚急性衰老模型小鼠学习与记忆能力的改善效应。方法小鼠皮下注射D-半乳糖构建亚急性衰老动物模型,分别给予阳性药多奈哌齐(2 mg·kg^(-1)·d^(-1))、杞参益智方低剂量组(1.33 g·kg^(-1)·d^(-1))、高剂量组(2.67 g·kg^(-1)·d^(-1)),连续给药30 d。通过水迷宫和Y迷宫实验评价模型小鼠学习与记忆行为;采用HE染色考察模型小鼠海马损伤情况;采用TUNEL法检测小鼠海马组织凋亡情况;采用ELISA法检测小鼠海马组织中氧化应激因子与炎症因子表达水平;采用Western blot法检测小鼠海马凋亡、氧化应激与炎性应激相关信号通路蛋白表达。结果杞参益智方水提取物显著缩短模型小鼠水迷宫测试中潜伏期和上台前路程(P<0.01),增加穿越平台次数(P<0.01);增加模型小鼠Y迷宫新臂探索时间和次数(P<0.05);抑制模型小鼠海马TUNEL荧光表达(P<0.01);上调氧化应激因子超氧化物歧化酶(SOD)活力(P<0.05)与谷胱甘肽(GSH)含量(P<0.05),下调丙二醛(MDA)含量(P<0.05);下调白细胞介素(IL)-1β、IL-6与肿瘤坏死因子(TNF-α)表达水平(P<0.05,P<0.01);下调凋亡信号通路蛋白Cleaved Caspase-3与Caspase-3表达(P<0.05),上调氧化应激信号通路蛋白Nrf2与HO-1表达(P<0.05),下调炎性应激信号通路蛋白p-NF-κB与NF-κB表达(P<0.05)。结论杞参益智方具有改善D-半乳糖注射亚急性衰老模型小鼠学习与记忆能力的作用,可能与其抑制海马氧化应激与炎性应激作用相关。OBJECTIVE To evaluate the effect of Qishen Yizhi formula on improving learning and memory ability in D-galactose subcutaneous injection induced subacute aging mice.METHODS Subacute aging mice model mice were developed by D-galactose subcutaneous injection and then treated with positive drug donepezil(2 mg·kg^(-1)·d^(-1))and Qishen Yizhi formula water extracts in low(1.33 g·kg^(-1)·d^(-1))and high dose group(2.67 g·kg^(-1)·d^(-1)).The learning and memory abilities of mice were evaluated using Morris water maze and Y maze tests;HE staining was used to examine hippocampal damage in model mice;TUNEL was used to detect apoptosis of mouse hippocampal tissue;ELISA was used to detect the expression levels of oxidative stress factors and inflammatory factors in the mouse hippocampus tissue;Western blot was used to detect the expression of signaling pathway proteins related to apoptosis,oxidative stress and inflammatory stress in the hippocampus of mice.RESULTS The water extract of Qishen Yizhi formula significantly shortened the latency and distance of model mice for reaching the platform in the water maze test(P<0.01),and significantly increased the number of crossing the platform(P<0.01);increased the exploration time and number of the Y maze new arm in model mice(P<0.05);inhibited the TUNEL fluorescence expression in the hippocampus of model mice(P<0.01);upregulated the activity of the oxidative stress factor superoxide dismutase(SOD)(P<0.05)and glutathione(GSH)content(P<0.05),and downregulated malondialdehyde(MDA)content(P<0.05);reduced interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF-α)expression levels(P<0.05,P<0.01);decreased the expression of apoptosis signaling pathway proteins Cleaved Caspase-3 and Caspase-3(P<0.05),upregulated the expression of oxidative stress signaling pathway proteins Nrf2 and HO-1(P<0.05),and downregulated the expression of inflammatory stress signaling pathway proteins p-NF-κB and NF-κB(P<0.05).CONCLUSION Qishen Yizhi formula can improve the learning and memory ability of su

关 键 词：杞参益智方 衰老 氧化应激 中枢神经炎症 

分 类 号：R285.5[医药卫生—中药学]