安徽医科大学学报2024,Vol.59Issue(10):1736-1741,6.DOI:10.19405/j.cnki.issn1000-1492.2024.10.007
拮抗P2X7受体在减轻子痫抽搐大鼠海马损伤中的作用
Role of antagonistic P2X7 receptor in reducing hippocampal damage in epileptic rats
摘要
Abstract
Objective To investigate the mechanism of purinergic ion channel receptor 7(P2X7)intervention in reducing hippocampal damage in epileptic convulsions.Methods A total of 28 SD female rats were divided into 4 groups(n=7 in each group)according to random number table method.The male and female rats were combined with 2:1 cage.The sperm cells observed by vaginal smear on day 2 were marked as day 0 of pregnancy(GD0),and the model of epileptic pregnant mice was prepared by injecting LPS into the tail vein of GD14 and PTZ into the abdomen continuously on GD16-18.The inhibitor group was prepared by intraperitoneal injection of P2X7 inhibi-tor(A-438079)immediately after intraperitoneal injection of PTZ in GD18.They were divided into:① normal pregnancy group(P group);② Epilepsy group(LPS+PTZ group);③ P2X7 inhibitor group(LPS+PTZ+A-438079 group);④ Eclampsia control group(LPS+PTZ+NS group).Racine scoring criteria were used to deter-mine the grade of epileptic seizure in rats to evaluate the degree of epileptic seizure in each group and record the duration of each phase.The expression levels of P2X7 and NLRP3 in the hippocampus of pregnant mice were de-tected by Western blot.The expression of TNF-α,IL-1 β,PIGF and sFlt-1 inflammatory factors in serum of preg-nant mice was determined by ELISA.Results The tic behavioral scores of rats in LPS+PTZ group and LPS+PTZ+NS group were significantly higher than those in P group.Compared with LPS+PTZ+A-438079 group,LPS+PTZ+NS group and LPS+PTZ+NS group,the first stage of seizure latency,the fifth stage of seizure latency and the duration of 1-4 stages of seizure decreased.Both the rate of stage 5 seizures and the duration of stage 5 sei-zures were prolonged.Western blot results showed that compared with LPS+PTZ group and LPS+PTZ+NS group,the expressions of P2X7 and NLRP3 in hippocampus of pregnant rats in LPS+PTZ+A-438079 group in-creased.ELISA results showed that compared with P group,serum inflammatory factor markers tumor necrosis fac-tor-α(TNF-α)and interleukin(IL)-1 β were detected in LPS+PTZ and LPS+PTZ+NS groups.Soluble FMS-like tyrosine kinase 1(sFlt-1),a marker of preeclampsia;placental growth factor(PIGF)increased,while P2X7 receptor inhibitors were used to reduce all indicators.Conclusion Intervention of P2X7 receptor may reduce the systemic inflammatory response of epileptic pregnant mice,reduce neurohippocampal damage,increase the convul-sive threshold,and inhibit the occurrence of epileptic convulsions.关键词
P2X7受体/子痫抽搐/海马损伤/炎症/炎症因子Key words
P2X7 receptor/convulsive eclampsia/hippocampus injury/inflammation/inflammatory factor分类
医药卫生引用本文复制引用
李晓晶,李晓兰..拮抗P2X7受体在减轻子痫抽搐大鼠海马损伤中的作用[J].安徽医科大学学报,2024,59(10):1736-1741,6.基金项目
国家自然科学基金项目(编号:81801477) National Natural Science Foundation of China(No.81801477) (编号:81801477)