山西医科大学学报2025,Vol.56Issue(9):1051-1056,6.DOI:10.13753/j.issn.1007-6611.2025.09.009
酸枣仁汤对GAD65相关癫痫的治疗效果
Therapeutic effect of Suanzaoren decoction on GAD65-related epilepsy
摘要
Abstract
Objective To investigate the antiepileptic effect of Suanzaoren decoction(SZRD)for glutamate decarboxylase-65(GAD65)associated epilepsy and its underlying mechanism.Methods Seventy mice were randomly divided into control group(n=10)and model group(n=60).The mice in model group were intravenously injected with murine GAD65 monoclonal antibody(100 μg/mL,0.1 mL)daily for 3 d.Then,these mice were intraperitoneally injected with pentylenetetrazol(PTZ,10 mg/kg)daily for 7 d to induce seizures.After the evaluation of seizure latency and severity,the mice with epileptic symptoms were randomly divided into five groups:model group,positive control group(phenytoin sodium,100 mg/kg),and Suanzaoren decoction(SZRD)low(10 g/kg),medium(25 g/kg),and high(50 g/kg)groups,with 10 mice in each group.The mice in positive control group were orally administrated with phenytoin sodium solution(10 mg/mL),while the mice in SZRD groups were treated with SZRD solution at the crude drug concentrations of 1,2.5,5 kg/L,respectively.The mice in model group and control group received saline.The treatment lasted 28 d.At days 1,7,14,21,28 of the treatment,the antiepileptic efficacy was assessed using the Racine seizure-severity scale.After the last behavior test,the mice were sacrificed to collect temporal cortex tissues.The contents of cytokines such as γ-aminobutyric acid(GAB A),gluta-mate(Glu),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and interleukin-10(IL-10)in the temporal cortex tissues were de-tected by kits,while the protein expressions of GAD65,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),phosphorylated nuclear factor κB(p-NF-κB),B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X(Bax)were detected by Western blot.Results Compared with control group,the mice in model group exhibited epileptic symptoms above Racine stage 3.Compared with model group,the mice showed a prolonged seizure latency and reduced seizure severity from day 7 in positive control group(P<0.05),and the mice in medium and high SZRD groups showed antiepileptic effects similar to that of positive control group(P<0.05),whereas the mice showed no any improvement.Compared with control group,the mice in model group showed decreased contents of GABA and IL-10(P<0.05),increased contents of Glu,IL-6,and TNF-α(P<0.05),downregulated expressions of GAD65 and Bcl-2 proteins(P<0.05),and elevated expressions ofNLRP3,p-NF-κB,and Bax proteins(P<0.05).Compared with model group,the mice in medium and high SZRD groups showed increased contents of GABA and IL-10(P<0.05),decreased contents of Glu,IL-6,and TNF-α(P<0.05),upregulated expressions of GAD65 and Bcl-2 proteins(P<0.05),and downregulated expressions of NLRP3,p-NF-κB,Bax proteins(P<0.05).Conclusion SZRD exerts a pronounced antiepileptic effect,which may be related to the upregulated GAD65 expression and the conversion of glutamate to GABA,and also related to the suppression of inflammation.关键词
酸枣仁汤/癫痫/GAD-65/γ-氨基丁酸/谷氨酸/炎症反应Key words
Suanzaoren decoction/epilepsy/GAD-65/γ-aminobutyric acid/glutamate/inflammatory response分类
医药卫生引用本文复制引用
张勖,寇晓文..酸枣仁汤对GAD65相关癫痫的治疗效果[J].山西医科大学学报,2025,56(9):1051-1056,6.基金项目
新疆维吾尔自治区重点实验室开放课题(XJDX711-2217) (XJDX711-2217)