丙戊酸通过调控S100B蛋白表达对癫痫幼鼠模型的认知功能及NMDAR1水平的影响  

Effects of valproic acid on cognitive function and NMDAR1 levels in juvenile epileptic rats by regulating S100B protein expression

作　　者：冯骄 黄丽 侯宁 谢南昌 陈敏 Feng Jiao;Huang Li;Hou Ning(Children's Hospital,Maternal and Child Health Care Hospital,Linfen Shanxi 041000)

机构地区：[1]山西省临汾市妇幼保健院儿童医院,041000

出　　处：《卒中与神经疾病》2023年第5期454-460,共7页Stroke and Nervous Diseases

基　　金：国家自然科学基金委员会资助项目(编号为81971214);徐州医科大学附属医院发展基金资助项目(编号为XYFM2021039)。

摘　　要：目的探讨丙戊酸通过调控S100B蛋白表达对癫痫幼鼠模型的认知功能及N-甲基-D-天冬氨酸受体(N-methyl-D-aspartate receptor,NMDAR)1水平的影响。方法50只幼鼠按随机数字表分为对照组、模型组、丙戊酸组、喷他脒(Pentamidine)组及丙戊酸+Pentamidine组,每组各10只;除对照组外,其余各组幼鼠均建立癫痫模型,建模后丙戊酸组灌胃1 mg/kg丙戊酸,Pentamidine组注射5 mg/kg的Pentamidine及丙戊酸+Pentamidine组灌胃1 mg/kg丙戊酸和尾部注射5 mg/kg的Pentamidine;水迷宫实验检测认知功能;尼氏染色观察海马组织形态;末端脱氧核苷酸转移酶介导的dUTP尾端标记法(Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling,TUNEL)法检测海马组织神经细胞凋亡率;免疫组化染色检测海马组织NMDAR1阳性细胞率;免疫印记检测海马组织中S100钙结合蛋白B(S100 calcium-binding protein B,S100B)、环氧化酶2(Cyclooxygenase-2,COX-2)及白细胞介素(Interleukin,IL)-1β蛋白表达水平。结果与对照组比较,模型组幼鼠第1、2、3及4 d搜索平台时间、神经细胞凋亡率、NMDAR1阳性细胞率及S100B,COX-2及IL-1β蛋白水平升高,穿越平台次数及原平台搜索时间占比均减少(P<0.05);与模型组比较,丙戊酸组幼鼠第1、2、3及4 d的搜索平台时间、神经细胞凋亡率、NMDAR1阳性细胞率及S100B,COX-2及IL-1β蛋白水平降低,穿越平台次数及原平台搜索时间占比增加(P<0.05);与丙戊酸组比较,Pentamidine组第1、2、3及4 d的搜索平台时间减少,穿越平台次数及原平台搜索时间占比增加,神经细胞凋亡率、NMDAR1阳性细胞率及S100B,COX-2及IL-1β蛋白水平无明显变化(P>0.05);与Pentamidine组比较,丙戊酸+Pentamidine组幼鼠第1、2、3及4 d的搜索平台时间、神经细胞凋亡率、NMDAR1阳性细胞率及S100B,COX-2及IL-1β蛋白水平降低,穿越平台次数及原平台搜索时间占比均增加(P<0.05)。结论丙戊酸可显著改善癫痫幼鼠模型�ObjectiveTo investigate the effects of valproic acid on cognitive function and NMDAR1 levels in juvenile epileptic rats by regulating S100B protein expression.Methods Fifty young rats were randomly divided into the control group,model group,valproic acid group,pentamidine group,and valproic acid plus pentamidine group with 10 rats in each group.Except for the control group,the epilepsy model was established in the other groups.After modeling,the VPA group was orally administered VPA(1 mg/kg)by gavage.The pentamidine group was injected through the tail vein with 5 mg/kg pentamidine.The valproic acid plus pentamidine group was orally administered 1 mg/kg valproic acid and injected with 5 mg/kg pentamidine through the tail vein.The water maze test was used to detect cognitive function.The morphology of the hippocampus was observed by Nissl staining.Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)was employed to determine the apoptotic rate.Immunohistochemical staining was used to detect NMDAR1-positive cells,S100 calcium-binding protein B(S100B),cyclooxygenase-2(COX-2),and interleukin(Interleukin,Il-1β)protein expression levels in the hippocampus.Results Compared with the control group,the platform searching time,nerve cell apoptotic rate,NMDAR1-positive cell rate,and S100B,COX-2 and IL-1βprotein levels were increased in the model group on day 1,day 2,day 3 and day 4,while the times of crossing the platform and the proportion of searching time on the original platform were decreased with statistical significance(P<0.05).Compared with the model group,the platform searching time,nerve cell apoptotic rate,NMDAR1-positive cell rate and S100B,COX-2 and IL-1βprotein levels of young mice in the valproic acid group decreased on day 1,day 2,day 3 and day 4,while the times of crossing the platform and the proportion of searching time on the original platform increased with statistical significance(P<0.05).Compared with the valproic acid group,the pentamidine group spent less time searching on da

关 键 词：幼鼠 癫痫 丙戊酸 认知功能 神经细胞 S100钙结合蛋白B N-甲基-D-天冬氨酸受体1 

分 类 号：R742.1[医药卫生—神经病学与精神病学]