柴胡疏肝汤抑制脑吲哚2,3-双加氧酶改善慢性颞叶癫痫大鼠的癫痫相关性抑郁样行为

Chaihushugan Decoction Improves Epilepsy- associated Depressive- like Behavior in Rats with Chronic Temporal Lobe Epilepsy by Inhibiting of Brain Indoleamine 2,3-dioxygenase

目的建立氯化锂-匹罗卡品慢性颞叶癫痫抑郁共病大鼠模型,探讨柴胡疏肝汤通过抑制脑吲哚2,3-双加氧酶(IDO1)治疗癫痫、改善癫痫相关性抑郁样行为的作用。方法腹腔注射匹罗卡品诱发大鼠癫痫持续状态(SE),约至第8周形成癫痫抑郁共病模型,表现出癫痫相关性抑郁样行为。将成功模型随机分为1-甲基-色氨酸(1-MT)组(A组),柴胡疏肝汤高、中、低剂量组(B组、C组、D组),生理盐水组(E组)。通过强迫游泳(FST)和蔗糖消耗实验检测抑郁行为的变化,实时荧光定量PCR(RT-q PCR)检测白细胞介素1β(IL-1β)、白细胞介素6(IL-6)和吲哚2,3-双加氧酶(IDO1)mRNA的表达,液相色谱-质谱法检测海马犬尿素(KYN)、色氨酸(TRY)及五羟色胺(5-HT)的浓度。结果慢性颞叶癫痫模型呈时间依赖性诱导海马IL-1β、IL-6的表达上调,进而激活IDO1,导致TRY代谢通路的改变,致使KYN浓度增加,5-HT浓度降低,最终诱发慢性颞叶癫痫相关的抑郁行为。柴胡疏肝汤通过抑制海马IDO1的激活阻止了慢性颞叶癫痫相关性抑郁样行为,减少癫痫自发发作次数。结论柴胡疏肝汤高、中剂量具有抑制脑IDO1的激活,改善大鼠癫痫相关性抑郁样行为,减少癫痫发作次数的作用。

Objective To establish lithium chloride-pilocarpine rat models of depression comorbid chronic temporal lobe epilepsy,explore the treatment of epilepsy,improve epilepsy- associated depressive- like behavior use of Chaihushugan decoction by inhibiting of brain indoleamine 2,3-dioxygenase1( IDO1). Methods Intraperitoneal injection of pilocarpine induced rat status epilepticus( SE),is about to 8 weeks of spontaneous development into epileptic depression comorbidity model,show the epilepsy- associated depressive-like behavior. Successful models were randomly divided into 1- MT group( group A),Chaihushugan decoction high,medium and low dose group( group B,C,D),and normal saline group( group E). By forced swimming( FST) and saccharine preference test( TPT) detection depression behavior change; By real-time fluorescent quantitative PCR( RT- q PCR) detection interleukin 1 beta( IL-1β),interleukin 6( IL-6) and IDO1 mRNA expression; By liquid chromatography-mass spectrometry detection dogs hippocampus ratio of urea( KYN) / tryptophan( TRY) and serotonin( 5- HT) / KYN ratio. Results Chronic temporal lobe epilepsy model assume the time dependence of inducing the hippocampus proinflammatory cytokines IL-1βincreases,the expression of IL-6,further leaed to the activation of IDO,the change of the metabolic pathways leading to TRY,caused KYN / TRY ratio increases,5- HT / KYN ratio is reduced,eventually leaed to the depression of chronic temporal lobe epilepsy related behavior. Chaihushugan decoction by inhibiting the activation of hippocampal IDO1 prevented chronic temporal lobe epilepsy correlation in depression behavior,reduced epilepsy attack frequency of spontaneous. Conclusion Chaihushugan decoction of high,middle dose can inhibit the activation of brain IDO1,improve in depression rats epilepsy- associated depressive-like behavior