| BackgroundEpilepsy is a common disease of the nervous system,which is a clinical syndrome caused by a variety of reasons that brain neurons highly synchronized abnormal discharge, it has seizures, transient, repetitive and stereotyped characteristics. The clinical manifestations including many aspects of movement, sensation, awareness, mental, behavioral and autonomic dysfunction,etc, when epileptic seizures. Long-term recurrent seizures not only harm the patient’s body, affect the quality of life of patients, but can lead to a range of psychological problems, result in a very heavy burden to society and family. Depression is a common mood disorder, which main clinical features with significant and persistent low mood, including a lack of interest, reduced activity, fatigue, weakness, slow thinking, difficulty concentrating, indecision, low self-evaluation, consider themselves useless, helpless and worthless, often self-accusation, sense of guit, recurring think the idea of death or suicidal behavior, loss of appetite or increased, weight loss or gain, insomnia or hypersomnia, etc. Until now, etiology of depression remains unclear, the combined effects of multiple factors may be the cause of depression, and biological factors that constitute predisposed or basic quality, psychological and social factors play a role in triggering. Epilepsy consolidation depression is common in clinical, Western medicine for epilepsy-depression comorbidity research is reported fewer in early, treatment is quite limited as well, but recent studies on epilepsy patients with depression has become a hotspot of clinical and basic research.There has been reported that the incidence of Epilepsy -depression comorbidity is between 9% and 62%. The incidence of depression in epilepsy patients was significantly higher than the general population. The latest meta-analysis to 29,891 patients with epilepsy who took part in nine studies showed that the incidence of epilepsy with depression among these subjects is 23.1%. Epilepsy merger mental disorders, especially depression is an important factor affecting the quality of life of patients. Depression can run through the whole epilepsy pathological process, not only affects the quality of life of patients with epilepsy, leading to recurrent seizures, but increases risk of suicide in epilepsy patients. Depression is recurrence after aggravating factor warning in temporal lobe epilepsy and mesial temporal lobe sclerosis patients 1 year after surgery. The risk of epilepsy patients with depression or develop drug resistance refractory epilepsy than those without depression were higher by 2.2 times and the rate of surgical treatment failure is higher. According to statistics, depression in the frontal, temporal lobe epilepsy patients prone, especially prevalent in patients with temporal lobe complex partial seizures. Therefore, explore the mechanism of epilepsy with depression and take positive and effective measures to control epilepsy-comorbid depression is important.Chronic temporal lobe epilepsy may occur in serum cortisol concentration, increase the expression of pro inflammatory cytokines interleukin-1β(IL-1β), interleukin -6 (IL-6), etc., resulting in 5-HT-axis imbalance, leading to hippocampal serotonin (5-HT) content is reduced,to 5-HT1A receptor down-regulation of expression, resulting in depression, epilepsy merger.5-HT-axis dysfunction may cause hypothalamic-pituitary-adrenal axis (HPA) disorders, thereby activating cytokines IL-1β, IL-6signaling pathway which affects epilepsy. Some studies suggest that certain anti-epileptic drugs can cause depression and other mental disorders, epilepsy and even lead to suicide. Another study showed that the use of antidepressants against certain aggravating can induce seizures. Epilepsy comorbid depression is common in clinical. Western medicine used in combination with antidepressants to treat epilepsy antiepileptic-there is a certain contradiction comorbid depression and risk, but clinical medicine "from the Liver" use Chaihu Shugan decoction to treat epilepsy comorbid depression and achieved satisfactory results. Chinese medicine have a little side effects, mild toxicity, and low price compose to clinical commonly used antiepileptic and antidepressant, and well tolerated in patients. The clinical application of Chinese medicine to treat epilepsy-depression comorbidity, to explore the mechanism of traditional Chinese medicine is very important. Currently, the influence of Chinese medicine for 5-HT content and IL-1β, IL-6mRNA expression on epilepsy comorbid depression in the hippocampus of rats have reported few studies. This paper aims to establish epilepsy comorbid depression rat model to investigate the impact of Chaihu Shugan decoction to 5-HT content and IL-1β, IL-6 mRNA expression in hippocampus of rats, and to explore the possible mechanism of action, thus for the clinical treatment of epilepsy-depression comorbidity provide experimental evidence.Epilepsy is a Chinese "Epilepsy", the depression is a Chinese "Yu disease" category, China’s ancient physicians have found that epilepsy is often accompanied by manifestations of emotional disorders in the long clinical practice, but emotional disorders often related to depression, anxiety and other "liver syndrome" is related to the performance of the main symptoms. Epilepsy and depression both have a common pathogenesis or "Qi stagnation." Professor Xie Wei is a modern TCM, he combined clinical and academic thought of ancient physicians put forword that "from the Liver" is the key to treat epilepsy-depression comorbidity; He proposed use of "Chaihu shugan decoction " to treatment of epilepsy-depression in the clinical process and achieved good results. Chaihu Shugan decoction is composed by Chaihu Guizhi decoction, matched into Si Wu decoction, combined raw keel, raw oysters, Uncaria. Prescription use Chaihu Guizhi decoction liver qi stagnation, qi and phlegm, Si Wudecoction Liver, liver, raw keel, raw oysters, Uncaria etc. towns liver yang, liver wind subsided, various drugs were Minato liver Liver, Softening Liver, liver-yang effect. However, the mechanism of Chaihu Shugan decoction action is not yet clear in the process of treatment epilepsy-depression. Therefore help of laboratory animals established to simulate the human epileptic seizures with depression-depression comorbidity animal model to investigate the possible mechanism of Chaihu shugan decoction has a very practical significance.Currently chronic temporal lobe epilepsy-depression model of rats have recognized worldwide, the main reasons include:(1) So far, the study about the lithium-pilocarpine chronic temporal lobe epilepsy and depression comorbidity model is more; (2) Some researchers who believe that "factors-stress" is one of the mechanisms lead to epilepsy-comorbid depression occurring. And this animal model conforms "factor-stress model"; (3) According to statistics, temporal lobe epilepsy is most common in clinical. Frontal temporal lobe epilepsy patients, especially temporal lobe complex partial seizures in patients with susceptibility depression; Most similar to the frontal lobe, temporal lobe epilepsy patients with SPECT, PET, EEG and other tests results in patients with depression. Using SPECT detection cortex (temporal lobe and frontal lobe) depressed patients, mostly shown to reduce its perfusion; Detecting frontal temporal lobe epilepsy corresponding lobe, found perfusion increased. These findings suggest that the amount of temporal lobe epilepsy and recurrent brain dysfunction is closely related to the occurrence of epilepsy-depression, while the lithium-pilocarpine model of chronic epilepsy has been proven to be an TLE model, so the model is consistent with the choice of our group spirit translational medicine; (4) Related to epilepsy-depression before research by the National Natural Science Foundation of the applicant is also based on this model, and the model is validated by experiments operable. The previous experimental results indicate that chronic temporal lobe epilepsy can develop and comorbid depression, therefore, use of this model to carry out the follow-up study has inherited.Therefore, our group through the establishment of lithium-pilocarpine chronic temporal lobe epilepsy-depression modle rats, to observe the effect of Chaihu Shugan decoction on the content of 5-HT, expression of IL-1β and IL-6mRNA on hippocampus in rats,and to explore the possible mechanism of Chaihu Shugan decoction.PurposeBased on the theoretical basis of this study, "From the Liver," the treatment of epilepsy-depression comorbidity and suppress proinflammatory cytokine expression on the 5-HT-axis. To observe the effect of Chaihu Shugan decoction on the content of 5-HT, expression of IL-1β and IL-6mRNA on chronic temporal lobe epilepsy and depression modle in hippocampus in rats. To explore the possible mechanism of Chaihu shugan decoction to treat epilepsy-depression comorbidity. For epilepsy depression comorbidity, "from the Liver" provide experimental evidence.Method1 Modeling, grouping, administration and related indicators detection methodFirst, with 75% ethanol injection site disinfection rat abdomen, then intraperitoneal injections of lithium chloride (130 mg.kg-1, dissolved in deionized water injection capacity of 1 mL.kg-1), after 24 hours, intraperitoneal injection of pilocarpine hydrochloride (40 mg.kg-1, dissolved in 0.9% sodium chloride injection, injection capacity of 1mL.kg-1), rats induced status epilepticus (SE).10-15min after pilocarpine injection can be observed persistent seizures in rats. According to Racine J grading standards, seizures amounted to 4,5-level degree and duration of more than two hours of rats can enter the next test by screening; To alleviate seizures, reduce rats died within 3 hours after the seizure and 8 h were injected with diazepam (5 mg.kg-1, dissolved in 0.9% sodium chloride injection, injection capacity of 2 mL.kg-1) and phenytoin (50 mg.kg"1, dissolved in 0.1M NaOH, injection capacity of 1 mL.kg-1) termination SE. After 8 weeks of observation, making a successful screening epilepsy-depression comorbidity model, and randomly divided into model group, citalopram, Chaihushugan decoction high, medium and low dose group. Normal 10. Drug intervention group were given citalopram 10 mg.kg-1.d-1, Chaihushugan decoction high, medium and low dose 10, 5,2.5 g. kg-1.d-1, the normal group and model group correspondence given saline ig, 4 weeks,2 times/d. By forced swimming (FST) and sucrose consumption test to assess depressive behavior change; video surveillance rat epileptic episodes;By liquid chromatography-mass spectrometry hippocampal 5-HT levels; By real-time PCR detect the expression of IL-1β,and IL-6 mRNAof hippocampal.2. Statistical MethodsUsing SPSS13.0 statistical package, measurement data with x±s, Model screening using a paired-t test. Between the groups were compared using ANOVA (One-way ANOVA) statistical processing. The number of epileptic seizures in rats with a single repeated measures ANOVA statistical processing. P<0.05 indicates a statistically significant, P<0.01 indicated statistically significant.Result1. The normal group and model group, all indicators for monitoring changesCompared with the normal group, model group were forced to swim cumulative immobility time significantly prolonged, sugar consumption reduce significantly, IL-1β mRNA expression increased significantly (P<0.01); 5-HT content decreased, IL-6 mRNA expression increased (P<0.05).2. Changes in drug intervention depressive behavior in rats after 4 weeksCompared with the model group, after four weeks of drug intervention, citalopram, Chaihu shugan decoction high, midium dose FST cumulative immobility time was shortened significantly, sugar consumption increased significantly (P<0.01); citalopram, Chaihu shugan decoction high dose group low dose group comparison with Chaihu shugan decoction low dose was statistically significant (P<0.01). Compared with pre-intervention, drug intervention after the index change was statistically significant(P<0.05). Citalopram group and Chaihu Shugan decoction high and middle dose group was not statistically significant (P> 0.05).3. Changes drug intervention in rats after four weeks the number of seizuresComparison with the model group, drug intervention 4 weeks, citalopram and Chaihu shugan decoction high dose can significantly reducing the number of epileptic seizures in rats (P<0.01). Citalopram and Chaihu shugan decoction high dose group compares with Chaihu shugan decoction low dose group was statistically significant (P<0.01). Differences in the number of seizures in rats administered before the model was not statistically significant (P>0.05). Citalopram group and Chaihu Shugan decoction high and middle dose group was not statistically significant (P> 0.05).4. After 4 weeks of drug intervention in hippocampal 5-HT content and IL-1β, changes in the expression ofIL-6 mRNA.Compared with the model group, after four weeks of drug intervention, citalopram group were significantly increased5-HT(P<0.01), Chaihu shugan decoction high dose group were increased 5-HT(P<0.05); citalopram and Chaihu shugan decoction high dose group IL-1β, IL-6 mRNA expression was significantly reduced (P<0.01). Citalopram group and Chaihu Shugan decoction high and middle dose group was not statistically significant (P>0.05).Conclusion1. High and medium dose of Chaihu Shugan Tang can reduce epilepsy comorbidity of depression in hippocampus of modle rats IL-1β, IL-6mRNA expression, promote the production of 5-HT, reduce the number of seizures in rats, improve depressive behavior.2. Compared with citalopram, Chaihu shugan soup high and mediumdose group to treat epilepsy-comorbid depression have similar effects. |
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