柴胡疏肝汤对癫痫-抑郁共病模型大鼠海马TNF-α及5-HT的影响

Effect of Chai-Hu Shu-Gan Tang on TNF-α and 5-HT in Hippocampus among Epilepsy–depression Comorbidity Rat Model

目的:通过观察柴胡疏肝汤对氯化锂-匹罗卡品慢性颞叶癫痫-抑郁共病模型大鼠TNF-α和5-HT含量的影响,探讨柴胡舒肝汤对TNF-α、5-HT参与癫痫抑郁共病机制的干预作用。方法:建立氯化锂-匹颞罗卡品慢性颞叶癫痫大鼠模型,造模完成6周后,随机分为5组:西酞普兰组(A)、生理盐水组(B)和柴胡疏肝汤高、中、低剂量组(C、D、E),连续灌胃给药4周,每天2次。干预前后,RT-PCR法检测大鼠海马TNF-α水平,液相色谱-质谱联用检测大鼠海马5-HT含量,通过强迫游泳和糖精偏好实验进行抑郁行为学监测,大鼠痫性发作次数通过录像监测系统24 h监测。结果:与干预前比较,药物干预后,A、C、D组大鼠痫性发作次数明显减少,强迫游泳累计不动时间明显缩短(P<0.01),糖水消耗量明显增加(P<0.01);与B组相比,A、C、D组药物干预后,大鼠海马TNF-αm RNA的表达明显下调(P<0.01),5-HT的含量明显增加(P<0.05,P<0.01);A与C、D组相比,均无明显变化。结论:TNF-α通过调节5-HT的水平参与癫痫抑郁共病的发病机制,柴胡疏肝汤具有下调慢性颞叶癫痫抑郁共病模型大鼠海马TNF-αm RNA表达,提高5-HT含量,减少大鼠痫性发作次数,改善抑郁行为的作用。

This study was aimed to investigate the effects of Chai-Hu Shu-Gan Tang （CHSGT） on levels of TNF-α and 5-HT in lithium chloride - pilocarpine caused epilepsy - depression eomorbidity rat model, in order to discuss the intervention effect of CHSGT on TNF-a and 5-HT in epilepsy - depression comorbidity. The lithium chloride - pilocarpine caused epilepsy - depression comorbidity rat model was established. After 6 weeks of animal establishment, rats were randomly divided into 5 groups, which were citalopram group （A）, physiological saline group （B）, CHSGT high dose group （C）, medium dose group （D）, and low dose group （E）. Intragastric administration was given for 4 weeks, twice a day. Before and after the treatment, RT-PCR was performed to detect hippocampal TNF-α levels. Liquid chromatography-mass spectrometry was performed to detect hippocampal 5-HT levels. Both forced swimming test （FST） and saccharin preference test were carried out to monitor the depressive behaviors of rats. In the meantime, 24 hours a day video camera surveillance were performed to record the number of seizures of rats. The results showed that after treatment, the number of seizures of rats were significantly reduced, the accumulative immobility time in FST was shortened, and the consumption of sucrose increased significantly （P 〈 0.01） in group A, C and D. Compared with group B, after the treatment, the expressions of hippocampal TNF-α mRNA of rats in group A, C, D were distinctly downregulated, with the level of 5-HT significantly increased （P 〈 0.05, P 〈 0.01）. Compared with group A, group C and D showed no significant changes. It was concluded that TNF-α played a role in the pathogenesis of epilepsy - depression comorbidity through mediating the level of 5-HT. High and medium doses of CHSGT can downregulate the expression of TNF-α mRNA in depression eomorbidity of chronic temporal lobe epilepsy, increase 5-HT level, reduce the number of seizures of rats, and improve depressive behaviors.