鬼针草水煎液改善LPS诱导中枢神经系统炎症所致小鼠学习记忆障碍的作用研究  

Effect of Bidens pilosa Decoction on Learning and Memory Impairment in Mice with Central Nervous System Inflammation Induced by LPS

作　　者：仇可可 高晓乐 马相宇 宫宇晴 王冬梅[1] 段冷昕[1] QIU Ke-ke;GAO Xiao-le;MA Xiang-yu;GONG Yu-qing;WANG Dong-mei;DUAN Leng-xin(Medical School,Henan University of Science and Technology,Luoyang 471003,China)

机构地区：[1]河南科技大学医学院,河南洛阳471003

出　　处：《中药材》2020年第7期1709-1715,共7页Journal of Chinese Medicinal Materials

基　　金：国家自然科学基金项目(81601225)。

摘　　要：目的:探索鬼针草水煎液对LPS腹腔注射诱导小鼠中枢神经系统炎症致学习记忆障碍的保护作用及可能机制。方法:将小鼠随机分为正常对照组、模型组及鬼针草水煎液低、中、高剂量组。避暗实验、新奇事物辨别实验及Morris水迷宫实验检测小鼠的学习记忆能力;试剂盒检测小鼠血清SOD、MDA、GSH水平;尼氏染色观察小鼠海马尼氏体数量和病理变化;免疫组化检测小鼠大脑海马区NF-κB、CHOP蛋白表达情况;Western blot检测炎症相关因子TNF-α、NLRP3、NF-κB、IL-1β,内质网应激相关因子ATF-4、CHOP,氧化应激相关因子NOX-2蛋白表达情况。结果:避暗实验、新奇事物辨别实验及Morris水迷宫实验均显示鬼针草水煎液可改善LPS诱导中枢神经系统炎症所致小鼠认知障碍,提高小鼠学习记忆能力;血清学指标显示,与正常对照组比较,模型组SOD、GSH活性显著降低,MDA含量显著升高(P<0.01),与模型组比较,鬼针草水煎液中、高剂量组SOD、GSH活性显著升高,MDA含量显著降低(P<0.05或P<0.01);尼氏染色结果显示模型组小鼠海马区细胞排列紊乱,不同浓度的鬼针草水煎液处理后,尼氏体数量有所增加,细胞凋亡数量减少;免疫组化结果显示模型组小鼠海马区NF-κB、CHOP蛋白表达显著升高(P<0.01),与模型组比较,不同剂量给药组小鼠海马区NF-κB、CHOP蛋白表达显著降低(P<0.01);Western blot结果表明模型组小鼠脑组织中TNF-α、NLRP3、NF-κB、IL-1β、ATF-4、CHOP、NOX-2蛋白表达显著升高(P<0.05或P<0.01),不同剂量给药组小鼠脑组织中上述蛋白表达均不同程度降低。结论:鬼针草水煎液可改善LPS诱导中枢神经系统炎症所致小鼠认知障碍,提高小鼠学习记忆能力,其机制可能与抑制NF-κB炎症相关通路及CHOP内质网应激相关通路,减轻氧化应激反应,抑制细胞凋亡有关。Objective:To explore the protective effect and possible mechanism of Bidens pilosa decoction on learning and memory impairment in mice with central nervous system inflammation induced by LPS.Methods:The mice were randomly divided into normal control group,model group and Bidens pilosa decoction low-,middle-and high-dose groups.The learning and memory ability of mice was detected by dark avoidance test,novelty discrimination test and Morris water maze test;The levels of SOD,MDA and GSH in serum were detected by kit;The Nissl number and pathological changes of hippocampus in mice were observed by Nissl staining;The expressions of NF-κB and CHOP protein factors in hippocampus of mice were detected by immunohistochemistry;The expressions of inflammatory related factors TNF-α,NLRP3,NF-κB,IL-1β,endoplasmic reticulum stress related factors ATF-4,CHOP and oxidative stress related factor NOX-2 proteins were detected by Western blot.Results:The dark avoidance test,novelty discrimination test and Morris water maze test showed that Bidens pilosa decoction could improve the cognitive impairment and learning and memory ability of central nervous system inflammation mice induced by LPS;In model group,the serological indexes showed that the activities of SOD,GSH were significantly decreased and the content of MDA was significantly increased than those in the normal control group(P<0.01).Compared with the model group,the activities of SOD,GSH in Bidens pilosa decoction middle-,high-dose groups were significantly increased and the content of MDA was significantly decreased(P<0.05 or P<0.01);The results of Nissl staining showed that the cells in the hippocampus of mice in the model group were disordered,and the number of Nissl increased and the number of apoptosis decreased after the treatment with different concentrations of Bidens pilosa decoction.The results of immunohistochemistry showed that the NF-κB,CHOP protein expression levels in the hippocampus of mice in the model group were significantly increased(P<0.01),compared

关 键 词：鬼针草水煎液 神经炎症 学习记忆障碍 脂多糖 内质网应激 

分 类 号：R285.5[医药卫生—中药学]