Pinellia Total Alkaloids Modulate the GABAergic System in Hippocampal Formation on Pilocarpine-Induced Epileptic Rats

• 来源期刊: 中国结合医学杂志（英文版）
• 年，卷（期）: 2020,（2）
• 页码范围: 138-145
• 页数: 8页
• 语种: 英文
• DOI: 10.1007/s11655-019-2944-7

摘要

Objective:To investigate the neuromodulatory effect of pinellia total alkaloids (PTA) on the gamma-aminobutyric acidergic (GABAergic) system in epileptic rats,and preliminarily evaluate the anti-epileptic effect of PTA.Methods:Ninety-one male Sprague-Dawley rats were randomized to a control group (n=17) or an epileptic group (n=74) using computer-generated random numbers.Status epilepticus (SE) was induced with pilocarpine in the epileptic group.Epileptic rats that survived SE were randomly divided into 4 groups,namely an epilepsy group (n=13),a topiramate (TPM,60 mg/kg) group (n=12),a high-dose PTA (800 mg/kg) group (n=12),and a low-dose PTA (400 mg/kg) group (n=10).Treatments were given intragastrically once daily for 14 days.The control group and epilepsy group received normal saline.Spontaneous recurrent seizures (SRSs) were monitored 8-h daily for 7 days after treatment.Then,the hippocampal formation tissues were collected.GABA level was measured using enzyme-linked immunosorbent assay.Protein and mRNA expression levels of glutamate decarboxylase 65 (GAD65),GABA transporter-1 (GAT-1),GABA transaminase (GABA-T),and GABAA receptor (GABAAR) α4,α5,γ2 and δ subunits were measured using Western-blotting analysis and quantitative polymerase chain reaction.Results:PTA lowered the incidence and frequency of SRS (both doses vs.the TPM group,P＞0.05).Compared with the epilepsy group,PTA increased the levels of GABA (both doses P＜0.01) and GAD65 (mRNA,800 mg/kg,P＜0.01),and suppressed the levels of GAT-1 (mRNA,800 mg/kg,P＜0.01;400 mg/kg,P＜0.05),GABA-T (mRNA,both doses P＜0.01),and GABAAR δ subunit (protein,800 mg/kg,P＜0.05) and γ2 subunit (protein,both doses P＜0.01).PTA upregulated the low-expressed mRNA levels of GABAAR α5 subunit (400 mg/kg,P＜0.01),δ subunit (800 mg/kg,P＜0.05),and γ2 subunit (400 mg/kg,P＜0.05).Conclusions:PTA regulated the GABAergic system through modulating GABA levels and the expression levels of GAD65,GAT-1,GABA-T,and GABAAR α4,α5,γ2 and δ subunits.PTA may exert antiepileptic effects on the pilocarpine-induced epilepsy model.