栀子苷减轻乙型脑炎病毒诱导的认知功能受损及其机制探讨  

Geniposide alleviates cognitive impairment induced by Japanese encephalitis virus and the exploration of the underlying mechanism

作　　者：金安松 钟莲梅[1] 徐春燕[2] 马瑞芳[3] 唐曙光 马智萍 JIN An-song;ZHONG Lian-mei;XU Chun-yan;MA Rui-fang;TANG Shu-guang;MA Zhi-ping(Department of Neurology,the First Affiliated Hospital of Kunming Medical University,Kunming 650031,China;Department of Rehabilitation,the Second Affiliated Hospital of Kunming Medical University,Kunming 650033,China;Department of Emergency,the Second Affiliated Hospital of Kunming Medical University,Kunming 650033,China;Department of Pain,Ganmei Hospital,Kunming First People's Hospital,Kunming 650224,China;Department of Neurology,Chuxiong People's Hospital,Chuxiong 675099,China)

机构地区：[1]昆明医科大学第一附属医院神经内科,昆明650031 [2]昆明医科大学第二附属医院康复科,昆明650033 [3]昆明医科大学第二附属医院急诊科,昆明650033 [4]昆明市第一人民医院甘美医院疼痛科,昆明650224 [5]楚雄市人民医院神经内科,楚雄675099

出　　处：《现代免疫学》2024年第6期500-505,共6页Current Immunology

基　　金：云南省重大科技专项计划(202102AA100061)。

摘　　要：为了探讨栀子苷(geniposide,GE)对乙型日本脑炎病毒(Japanese encephalitis virus,JEV)诱导的认知障碍相关神经症状的潜在保护作用及其机制,为乙型日本脑炎(Japanese encephalitis,JE)的治疗提供新思路,将80只雄性BALB/c小鼠随机分为对照组、GE组、JEV感染组及GE治疗组,每组20只。统计各组小鼠14 d存活率;采用莫里斯水迷宫试验检测各组小鼠认知记忆能力;免疫荧光法检测海马区脑组织JEV感染情况;ELISA检测海马区脑组织炎症损伤和氧化应激水平;Western blotting检测自噬相关蛋白5(autophagy-related protein 5,Atg5)、B淋巴细胞瘤2(B-cell lymphoma 2,Bcl-2)、Bcl2相关X蛋白(Bcl2-associated X protein,Bax)、p62及微管相关蛋白轻链3(microtubule-associated protein light chain 3,LC3)-Ⅱ/LC3-Ⅰ表达。结果显示,GE治疗能够提高JEV模型小鼠的14 d存活率;与JEV感染组比较,GE治疗组小鼠的逃生潜伏期显著缩短,平台象限滞留时间比和穿越平台次数显著增加(P<0.01)。与JEV感染组比较,GE治疗组小鼠的JEV阳性细胞百分比显著降低(P<0.01)。与JEV感染组比较,GE治疗组小鼠IL-1β、TNF-α、活性氧(reactive oxygen species,ROS)和丙二醛(malondialdehyde,MDA)的表达水平显著降低(P<0.01),Atg5、Bax及LC3-Ⅱ/LC3-Ⅰ表达水平显著降低(P<0.01),p62和Bcl-2表达水平显著升高(P<0.01)。该研究提示,GE可抑制JEV诱导的小鼠死亡和学习认知功能障碍,该作用可能是通过减少氧化应激反应和炎症反应、改善自噬的过度激活而实现的。The aim of this study is to investigate the potential protective effect and the underlying mechanism of geniposide(GE)on neurologic symptoms related to cognitive impairment induced by Japanese encephalitis virus(JEV),which will provide new ideas for the treatment of Japanese encephalitis(JE).Eighty male BALB/c mice were randomly divided into control group,GE group,JEV-infected group,and GE-treated group,with 20 mice in each group.Subsequently,the 14-day survival rate of mice in each group was measured.The Morris water maze experiment was used to test the cognitive memory ability of mice in different groups.Immunofluorescence was used to detect JEV infection in the hippocampus of brain tissue.ELISA was used to detect the level of inflammatory damage and oxidative stress in the hippocampus of brain tissue.Western blotting was used to detect the protein expressions,including autophagy-related protein 5(Atg5),B-cell lymphoma 2(Bcl-2),Bcl2-associated X protein(Bax),p62,and microtubule-associated protein light chain 3(LC3)-Ⅱ/LC3-Ⅰ.The results showed that GE treatment improved the 14-day survival rate of JEV model mice.Compared to those of the JEV-infected group,the escape latency of GE-treated group was significantly shorter,platform quadrant retention time ratio and the number of platform crossing were significantly increased(P<0.01).Compared to that of the JEV-infected group,the percentage of JEV positive cells of GE-treated group was significantly decreased(P<0.01).Compared to those in the JEV-infected mice,the expressions of IL-1β,TNF-α,reactive oxygen species(ROS),and malondialdehyde(MDA)were significantly decreased in GE-treated mice(P<0.01).The expressions of Atg5,Bax,and LC3-Ⅱ/LC3-Ⅰin the GE-treated group were significantly lower(P<0.01),while the expressions of p62 and Bcl-2 were significantly higher(P<0.01).Taken together,this study shows that GE treatment may reduce mortality and improve learning and cognitive function in JEV-infected mice.The underlying mechanism may be the reduction of oxidative

关 键 词：栀子苷 脑炎病毒 炎症 自噬 

分 类 号：R512.32[医药卫生—内科学] R392.11[医药卫生—临床医学]