中医药导报2025，Vol.31Issue(9)：24-31,8.DOI:10.13862/j.cn43-1446/r.2025.09.004
痫得安丸联合丙戊酸钠通过TNF-α/NF-κB信号通路对癫痫大鼠神经元损伤和炎症的影响
Effects of Xiande'an Pill(痫得安丸)Combined with Sodium Valproate on Neuronal Injury and Inflammation in Epileptic Rats through TNF-α/NF-κB Signaling Pathway
摘要
Abstract
Objective:To explore the effects of Xiande'an pill combined with sodium valproate on neuronal injury and inflammation in epileptic rat models through the tumor necrosis factor-α(TNF-α)/nuclear factor-κB(NF-κB)signaling pathway.Methods:Epileptic rat models were established by combined injection of lithium chloride and pilocarpine.Totally 40 successfully modeled epileptic rats were randomly divided into model group,sodium valproate group[0.072 g/(kg·d)],Xiande'an pill group[1.350 g/(kg·d)],and Xiande'an pill[1.350 g/(kg·d)]+sodium valproate[0.072 g/(kg·d)]combination group(combination group).Another 10 healthy rats were used as the control group.After 4 weeks of administration,the frequency and duration of epileptic seizures in each group were recorded.Hematoxylin-eosin staining and Nissl staining were used to observe the pathological changes in the hippocampus.The levels of glutamic acid(Glu),γ aminobutyric acid(GABA),TNF-α and inter-leukin-1 β(L-1β)in serum and brain were detected.The expressions of TNF-α mRNA,tumor necrosis factor receptor 1(TNFR1)mRNA,NF-κB p65 mRNA,cyclooxygenase 2(COX-2)mRNA and matrix metalloproteinase 9(MMP-9)mRNA in the hippocampus were detected by RT-qPCR and Western blotting was used to detect the expressions of TNF-α,TNFR1,NF-κB p65,phosphorylated p65(p-p65),COX-2 and MMP-9 protein.Results:The model group showed higher frequency of epileptic seizures than control group(P＜0.01),and longer duration of epileptic seizures than control group(P＜0.01).The sodium valproate group,Xiande'an pill group and combination group showed lower frequency of epileptic seizures than model group(P＜0.01),and shorter duration of epileptic seizures than model group(P＜0.01).The combination group rats showed shorter duration of epileptic seizures than Xiande'an pill group(P＜0.01).The pyramidal neurons in the hippocampal CA1 region of the control group rats were arranged tightly and neatly,with clear structure and uniform staining,and abundant Nissl bodies in the cytoplasm.The pyramidal neurons in the hippocampal CA1 area were disordered in arrangement,and the cells atrophied in model group.The staining deepened in model group.The number of Nisslakosomes was significantly reduced.The pyramidal neurons in the CA1 region of the hippocampus are arranged more neatly and stained uniformly in the sodium valproate group,Xiande'an pill group and combination group,with an increase in the number of Nissl bodies and a morphology similar to the control group.The model group showed lower serum GABA content than control group(P＜0.01),while higher serum Glu,Glu/GABA,IL-1β and TNF-α than control group(P＜0.01).Sodium valproate group,Xiande'an pill group and combination group showed lower serum Glu,Glu/GABA,IL-1β and TNF-α than model group(P＜0.05 or P＜0.01).The model group showed lower GABA content in brain than control group(P＜0.01),while higher serum Glu,Glu/GABA,IL-1β and TNF-α in brain than control group(P＜0.01).Sodium valproate group and Xiande'an pill group showed lower brain Glu/GABA than model group(P＜0.05).Combination group showed lower Glu,TNF-αand Glu/GABA in brain,than model group(P＜0.05 or P＜0.01).The model group showed higher relative expression levels of TNF-α mRNA,TNFR1 mRNA,NF-κB p65 mRNA,COX-2 mRNA and MMP-9 mRNA than control group(P＜0.01).Sodium valproate group showed lower relative expression levels of TNF-α mRNA and MMP-9 mRNA than model group(P＜0.05).Xiande'an pill group and combination group showed lower TNFR1 mRNA,COX-2 mRNA,MMP-9 mRNA,TNF-α mRNA and NF-κB p65 mRNA than model group(P＜0.05 or P＜0.01).The model group showed higher relative expression levels of TNF-α,TNFR1,p-p65,COX-2 and MMP-9 protein than control group(P＜0.05 or P＜0.01).Sodium valproate group showed lower relative expression levels of TNF-αand TNFR1 protein than model group(P＜0.05).Xiande'an pill group showed lower TNF-α,TNFR1 and COX-2 protein than model group(P＜0.05 or P＜0.01).Combination group showed lower TNF-α,TNFR1,p-p65,COX-2 and MMP-9 protein than model group(P＜0.01).Conclusion:Xiande'an pill combined with sodium valproate can reduce the occurrence of epilepsy in rats,improve pathological injury,protect neurons and reduce inflammatory response of epileptic rats,the mechanism of which is related to inhibiting TNF-α/NF-κB signaling pathway.关键词
癫痫/痫得安丸/丙戊酸钠/神经元/炎症/肿瘤坏死因子α/核因子κB/大鼠Key words
epilepsy/Xiande'an pill/sodium valproate/neurons/inflammation/TNF-α/NF-κB/rat分类
医药卫生引用本文复制引用
梁政娆,娄勍,甘海宁,黄晓丹..痫得安丸联合丙戊酸钠通过TNF-α/NF-κB信号通路对癫痫大鼠神经元损伤和炎症的影响[J].中医药导报,2025,31(9):24-31,8.基金项目
广东省中医药局科研基金重点项目(20223024) （20223024）
第五批全国中医临床优秀人才研修项目(国中医药人教函[2022]1号) （国中医药人教函[2022]1号）
