[1]冯骄,黄丽,侯宁,等.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[J].卒中与神经疾病杂志,2023,30(05):454-460.[doi:10.3969/j.issn.1007-0478.2023.05.006]
　Feng Jiao,Huang Li,Hou Ning,et al.Effects of valproic acid on cognitive function and NMDAR1 levels in juvenile epileptic rats by regulating S100B protein expression[J].Stroke and Nervous Diseases,2023,30(05):454-460.[doi:10.3969/j.issn.1007-0478.2023.05.006]
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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()
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《卒中与神经疾病》杂志[ISSN:1007-0478/CN:42-1402/R]

卷:
第30卷
期数:
2023年05期
页码:
454-460
栏目:
论著
出版日期:
2023-10-20

文章信息/Info

Title:
Effects of valproic acid on cognitive function and NMDAR1 levels in juvenile epileptic rats by regulating S100B protein expression
文章编号:
1007-0478(2023)05-0454-07
作者:
冯骄; 黄丽; 侯宁; 谢南昌; 陈敏
041000 山西省临汾市妇幼保健院儿童医院[冯骄 黄丽(通信作者)侯宁 谢南昌 陈敏]
Author(s):
Feng Jiao;  Huang Li;  Hou Ning;  et al.
Children's Hospital, Maternal and Child Health Care Hospital, Linfen Shanxi 041000
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
Keywords:
Epilepsy Valproic acid Cognitive function Nerve cell S100B NMDAR1
分类号:
R742.1
DOI:
10.3969/j.issn.1007-0478.2023.05.006
文献标志码:
A
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的认知功能,降低NMDAR1表达水平,减少神经细胞凋亡,其机制可能与调控S100B表达有关。
Abstract:
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-1β protein 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-1β protein 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 days 1, 2, 3 and 4, and the number of platform crossings and the time spent searching for the original platform were increased. There was no significant difference in the apoptotic rate of nerve cells, the rate of NMDAR1-positive cells or the protein expression of S100B, COX-2 and IL-1β between the valproic acid group and the pentamidine group(P>0.05). Compared with the pentamidine group, the platform searching time, nerve cell apoptotic rate, NMDAR1-positive cell rate and protein levels of S100B, COX-2 and IL-1β in the valproic acid plus pentamidine group decreased on day 1, day 2, day 3 and day 4, and the times of crossing the platform and the proportion of searching time on the original platform were increased, and the differences were statistically significant(P<0.05).Conclusion Valproic acid can significantly improve cognitive function, reduce the expression of NMDAR1 and inhibit the apoptosis of nerve cells in juvenile epileptic rats, and the mechanism might be related to its regulation of S100B expression.

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备注/Memo

备注/Memo:
基金项目: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)
更新日期/Last Update: 2023-10-20