Role of antagonistic P2X7 receptor in reducing hippocampal damage in epileptic rats

Acta Universitatis Medicinalis Anhui 2024 年 10 期 ;     font:big middle small

Found programs: National Natural Science Foundation of China (No.81801477)

Authors:Li Xiaojing; Li Xiaolan

Keywords:P2X7 receptor;convulsive eclampsia;hippocampus injury;inflammation;inflammatory factor

DOI:DOI:10.19405/j.cnki.issn1000-1492.2024.10.007

〔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 inhibitor(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 determine 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 detected by Western blot. The expression of TNF-α, IL-1β, PIGF and sFlt-1 inflammatory factors in serum of pregnant 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 seizures 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 increased. ELISA results showed that compared with P group, serum inflammatory factor markers tumor necrosis factor-α(TNF-α) and interleukin(IL)-1β 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 convulsive threshold, and inhibit the occurrence of epileptic convulsions.