| BackgroundEpilepsy is chronic recurrent transient cerebral dysfunction syndrome and is characteristic of abnormal discharge of neurons in the brain caused by temporary dysfunction; it is the common on disease to lose consciousness.lt has clinical characteristics of onset, transient, repeatability, epilepsy is significantly associated with depression, at least 30% epilepsy patients occurring with depression, depression is the most significant factors affect the quality of lives; major depression is one of the main reasons for epilepsy patients committed suicide. Depression in people with epilepsy seizures can appear in before, after, or during the attack. Control of the clinical seizure of patients with depression is not often ideal; depression can runs through the whole pathological process of epilepsy disease, and influence the degrees, durations, curative effects and so on.Epilepsy and depression comorbidity early view, the mechanism of epilepsy attack repeatedly, occur depression to patients with the increase of social and mental pressure.But the recent clinical studies gradually realize the emotional disorder, including depression, is the result of with all sorts of brain damage. Experimental animals can appear kind of modern disorders after 8 days being status epilepticus, and the pathological manifestations of epilepsy with depression show the decreases of the volume of hippocampal, the pathological damage of amygdala nerve and abnormal function of HPA. There are pathways of nervous regulation which give priority to with 5-HT can neural signaling pathways, and 5-HT takes part in immune regulatory as the same time, through the activation of the sympathetic nervous system, involved in regulating immune cell activity, influence the expression of the release of cytokines and antibody, which affect epilepsy.Therefore, how to correct and effective prevention and treatment of epilepsy-depression comorbidity widely concerned by the medical profession. But at present, in the treatment of epilepsy and depression comorbidity clinically still given priority to with oral antiepileptic drugs, joint taking antidepressant medication is complementary. A lot of evidences showing 5-HT have antiepileptic effect, safe and effective in patients with epilepsy, citalopram reduces even more than 50% of the morbidity, however some researches considered antidepressants 5-HT reuptake inhibitors of the risk of inducing epilepsy, clinically most antidepressants indicate the epilepsy patients with caution, and resistance to the treatments. Traditional Chinese medicine treatment of this disease shows unique advantages, epilepsy patients treated from liver treatment, not only antiepileptic effect, also can adjust the depression, at the same time it also possess the characteristic like slow action, prolonged, less side effects and low toxic side effects. This topic through treated from liver, by observing the contents of TNF-a and 5-HT in comorbidity of epilepsy-depression model rats by effecting from ChaiHuShuGanTang(CHSGT), reveal the role of TNF-α mediated 5-HT activity in the pathogenesis of Depression comorbidity of epilepsy, and the intervention effects from Chaihushugantang (CHSGT), to provide experimental basis to the Chinese medicine treatment of epilepsy and depression comorbidity.Epilepsy in traditional Chinese medicine belong to the category of "chronic disease", the past dynasties doctors found in clinical performance that epilepsy patients often accompanied by modern disorders, and disorders such as depression, anxiety, "liver" related syndromes, performance related to the pathogenesis of chronic disease and closely related to the pathogenesis of liver function abnormal, the produce of the wind, phlegm, stasis are the etiological and pathological from liver losing catharsis, therefore treated from liver is the key to treatment of epilepsy, depression comorbidity.ObjectiveBy investigating the effects of Chaihushugantang (CHSGT) on the levels of TNF-αand 5-HT in lithium chloride-pilocarpine caused epileptic -depression rats model, wewant to reveal the role of TNF-α mediated 5-HT activity in the pathogenesis of Depression comorbidity of epilepsy, and the intervention effects from Chaihushugantang (CHSGT). This experiment base on the "Treatments from liver theory", through the observation of ChaiHuShuGanTang(CHSGT) on lithium chloride-pilocarpine chronic temporal lobe epilepsy-depression model rats with the influence of the content of TNF-αand 5-HT, explore the ChaiHuShuGanTang(CHSGT) of TNF-αand 5-HT in epilepsy-depression comorbidity mechanism of intervention effect and the possible pathways and mechanisms, to provide experimental basis for traditional Chinese medicine theory of epilepsy-depression comorbidity "Treatments from liver theory".Methods1.experimental method6-weeks after successfully generatinglithium chloride pilocarpine caused epileptic-depression rats model, the rats were randomly divided into 5 groups:Group A treated with citalopram, Group B treated with physiological saline, and Group C, D, E treated with high, medium and low doses of CHSGT, respectively. The gavage treatments were givencontinuously twice a day for 4 weeks. Before and after the treatment, Real-time Reverse Transcription PCR was performed to detect hippocampal TNF-α levels; Liquid chromatography-Massspectrometry was performed to detect hippocampal 5-HT levels; Both Forced swim test (FST)and Saccharin preference test were carried out to monitor the depressive behaviors of rats;In the meantime,24 hours/day surveillance by video camera were performed to record the number of recurrent seizures of rats.2.Statistical methodUsing SPSS 13.0 statistical package, measurement data with x±s, model selection using matching t test. Comparison between groups using single factor analysis of variance (One-way ANOVA) statistical processing, number of seizures in rats using a single repetitive measure analysis of variance in statistical processing, P < 0.05 said statistically significant, P< 0.01 said significant statistical significance. Analyzing TNF-a and 5-HT correlation by using bivariate correlation, Spearman correlation coefficient rs= 0.732, P< 0.01.Results1.The depression model rats before and after drug intervention behavior changesCompared with before intervention, drug intervention after citalopram group, high dose group, medium dose group FST total motionless time was obviously shortened (P< 0.01); After the intervention citalopram group compared with normal saline group, total motionless time from citalopram group was obviously shortened, with statistical significance (P< 0.01); High, medium and low dose group compared with normal saline group, high, medium dose group of total motionless time significantly shortened, with statistical significance (P< 0.01), low dose group, no significant difference between the total motionless time, no statistical significance (P > 0.05); Citalopram groups with high, medium dose group was no significant difference (P> 0.05); High, medium and low dose group compared total motionless time with high, medium dose group was obviously less than the low dose group, with statistical significance (P< 0.01)。Compared with before intervention, drug intervention after citalopram group, Chinese medicine high, medium dose group of saccharin water consumption increased significantly (P< 0.01); After the intervention citalopram group compared with normal saline group, citalopram group of sugar water consumption increased significantly, with statistical significance (P< 0.01); High, medium and low dose group compared with normal saline group, sugar water consumption of high, medium dose group increased significantly, with obvious statistical significance (P< 0.01), low dose group of total motionless time shortened, with statistical significance (P< 0.05); Citalopram group compared with high, medium dose group no significant difference (P> 0.05); Traditional Chinese medicine (TCM) high, medium and low dose group compared with each other, sugar water consumption of high and medium dose groups are higher than the low dose group, no statistical significance (P> 0.05).2.Before and after drug intervention model the changes in the number of seizures in ratsCompared with before intervention,4 weeks after medication, seizures in rats from citalopram group, high dose group, medium dose group significantly reduced (P < 0.01)。Citalopram group compared with normal saline group, fewer seizures in citalopram group, with statistical significance (P< 0.01); Chinese medicine high, medium and low dose group compared with normal saline group, high, medium dose group of epileptiform seizure frequency decrease, with statistical significance (P< 0.01), no significant change in low dose group of epileptiform seizure frequency, no statistical significance (P> 0.05); Citalopram group compared with high, middle dose group no significant difference (P> 0.05); High, medium and low dose group compared with each other, epileptiform seizure frequency of high, middle dose group was obviously less than the low dose group, with statistical significance (P< 0.01).High, middle dose group of the curative effect of epileptic seizure frequency higher than the low dose group, low dose group curative effect is poorer.Before intervention, model rats there were no statistically significant difference number of seizures, with no statistical significance (P> 0.05).3.For 4 weeks after treatment rat hippocampal changes in concentrations of 5-HT4weeks after the treatment, citalopram group, high and middle dose group all got higher content of 5-HT. Citalopram group compared with normal saline group, the content of 5-HT citalopram group was obviously increased, with statistical significance (P< 0.01); High, medium and low dose group compared with normal saline group, high, middle dose group of 5-HT content increased, with statistical significance (P< 0.05), low dose group of 5-HT content was not significant, no statistical significance (P> 0.05); Citalopram group, high dose group and middle dose group compared with each other was no significant difference (P>0.05); high, medium and low dose group compared with each other, high, middle dose group 5-HT contents are higher than low dose group, with statistical significance (P< 0.05).4.For 4 weeks after dosing TNF-a mRNA in rat hippocampal fluorescence quantitative PCR electrophoresis result set expression quantityAfter intervention, citalopram group compared with normal saline group, citalopram group significantly reduce the amount of TNF-α mRNA expression, with statistical significance (P< 0.01); High, medium and low dose group compared with normal saline group, high, middle dose group less of TNF-α mRNA expression, with statistical significance (P< 0.01), low dose group decreased of TNF-α mRNA expression is not obvious, with no statistical significance (P> 0.05); Citalopram group, high and middle dose group compared with each other was no significant difference(P> 0.05); High, medium and low dose group compared with each other, high, middle dose group of TNF-a mRNA expression is better(more) than that of low dose group, with statistical significance (P< 0.01).ConclusionIn this experiment successfully establish lithium chloride-pilocarpine co-morbid chronic temporal lobe epilepsy-depression model, stability is good, prepare the way for follow-up studies.2.By adjusting the level of 5-HT to participate in the pathogenesis of epilepsy-depression comorbidity, Chaihushugantang (CHSGT) of high, middle dose have cut co-morbid chronic temporal lobe epilepsy depression model rats hippocampal TNF-a mRNA expression, increase the content of 5-HT, reduce the number of seizures in rats, improve behavior of depression. |
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