| Objective and significanceEpilepsy is chronic and disorders of recurrent seizures, which due to neuron discharge abruptly and intermittently, induce transient Cerebral Functional disorder that recurrent attacks. It can't be ignore that problem of medical treatment, family and social problem induced by epilepsy.The epilepsies, affect about 1% of the population worldwide. Available therapy is symptomatic in that drugs inhibit seizures but are not disease-modifying; that is, no effective pharmacological prevention or cure has been identified. The term epileptogenesis refers to the process by which a normal brain becomes epileptic.In now, epileptic treatment still dependent on chemicals, general anti-epileptic drug(AEDs) can control epileptic attack from 70% to 80%,but security is a problem in treatment of long-term, and the method to treat refractoriness epilepsy by surgery be confined by indication, high risk, expensive, and possible to recur. So epileptic treatment still dependent on chemicals, and the original AEDs is needed urgently. But it must know clearly that is pathogenesy of epilepsy before develop new AEDs.For the past few years, research of reepileptic pathogenesy has been advanced. Increase in neuronal excitability and synchronize firing is two important characteristic of epileptic, which had be generally accepted. Many scholars try them best to study mechanism of form, and introduced many view. Recognition of exist of "the network of immuno-neuro-endocrine" and relation of astrocyte with synaptic signal transmission have been gradually clear.The view of "the network of immuno-neuro-endocrine" proposed that system of immune, nerves and endocrine exist in organism of human, and the three systems have influence and bidirectional modulatory circuit in each other. Thus, the network was constituted, which closely related with pathogenesy of epilepsy. Research on epilepsy from the system of immune and endocrine can be regard as breakthrough. The system of immune and endocrine can modulate nervous system by the neuronal active compound, hormone and so on, and it can modulate normal neuronal physiological functions or epileptic morbidity. IL-6 is cytokine and very importent active factors, which be found abnormally express in epilepsy. Thus, the importent effects of IL-6 on epilepsy were found. IL-6 can modulate nerve injury, so it was emphasized. With the view of "the network of immuno-neuro-endocrine" introduced, the effects of astrocyte that majority in central nervous system have been gradually clear, Astrocytes can become reactive gliosis when nervous system have been damaged. Histologic characteristics of reactive gliosis is greaten and hyperplasia of astrocyte, biochemical marker is increase in content of glial fibrillary acidic protein(GFAP)of astrocyte. The reactive gliosis have effect on synaptic transmission that exciting neuronal by many kinds of pathway, and is epileptogenous.It is well known that Pharmacodynamic action of saikosaponin a (SSa) have anti-inflammatory, immunological regulation, promoting secrete of corticosterone. In the past research, we have found that saikosaponins and saikosaponin a can inhibit experimental epilepsy; saikosaponins can inhibit expression of glial fibrillary acidic protein and modulate expression of Glu and GABA in hippocampus. So, We suppose that saikosaponin a may inhibit experimental epilepsy by inhibit the effect of cytokine on nervous system and reactive gliosis.Based on the above, the objective of this research is to study on the effect of IL-6 that excesssive express in the central nervous system on electrical activity of rats brain and reactive gliosis and to observe the role of SSa.Method and content1. The effect of IL-6 on electrical activity of rats brain and the role of SSa.Twenty four healthy Sprague-Dawley rats were randomly divided into four groups with six in each group: Group A, Normal Sodium (NS+NS) group; Group B blank group(NS+IL-6); Group C, group of High-dose Saikosaponin a(1.81mg/kg, SSa+IL-6); Group D, group of Small-dose Saikosaponin a(0.91mg/kg, SSa+IL-6). Rats were injected the pretreatment medicine by intraperitoneal (Group A and Group B: NS 3ml/kg; Group C: the solution of SSa 1.81mg/kg; Group D: the solution of SSa 0.91mg/kg), IL-6 was injected by lateral cerebral ventricle after 30 minutes, and imbedment electrode in rats brain. Multichannel physiograph was applied in record rats electroencephalogr(EEG), unipolar lead, narcotism(record time 1h, 2h, 4h, 8h, 12h, 24h), land counted the sharp wave, computed the power and amplitude of the high-frequency(100Hz)wave.2. The effect of IL-6 on expression of rats hippocampal glial fibrillary acidic protein (GAFP) and the role of SSa.Fourty four healthy Sprague-Dawley rats were randomly divided into three groups: Group A, Normal Sodium (NS+NS) group, four rats; Group B, blank group(NS+IL-6), twenty rats; Group C, group of Saikosaponin a(1.81mg/kg, SSa+IL-6), twenty rats. Rats were injected the pretreatment medicine by intraperitoneal(Group A and Group B: NS 3ml/kg; Group C: the solution of SSa 1.81mg/kg), In group B and group C, IL-6 was injected by lateral cerebral ventricle after 30 minutes, and to obtain the sample of brain tissue on time 1h, 4h, 8h, 12h, 24h, four rats on each time, the technique of western-blot was applied in detect the expression of GFAP, and last, the result of western-blot was analyzed, and demonstrated in value of gray scale, and calculate the ratio of the value of gray scale of GFAP with the value of gray scale of GAPDH.Result1.The effect of IL-6 on electrical activity of rat's brain and the role of SSa(1) In four groups, the sharp wave were induced by IL-6, and the Group A and Group C have significant difference compare with the Group B at times of lh, 4h, 8h, 12h(P＜0.05), but except Group D. The dynamic change of the four groups sharp wave, Group A have significant difference compare with the 1h only at time of 12h (P＜0.05), Group B have significant difference compare with the lh at times of 4h, 8h, 12h, 24h (P＜0.05), the change of Group C wasn't significant (P＜0.05), Group D have significant difference compare with the 1h only at times of 2h (P＜0.05).(2) In four groups, the power of the high-frequency(100Hz)wave were raised by IL-6, and the Group A and Group C have significant difference compare with the Group B at times of lh, 4h, 8h, 12h(P＜0.05), but except Group D. The dynamic change of the four groups power of the high-frequency(100Hz)wave, Group A have significant difference compare with the 1h at times of 4h, 8h, 12h(P＜0.05), Group B have significant difference compare with the lh at times of4h, 8h, 12h, 24h (P＜0.05), Group C have significant difference compare with the 1h at times of 4h, 8h(P＜0.05), Group D have significant difference compare with the lh only at times of 8h(P＜0.05).(3) In four groups, the amplitude of the high-frequency(100Hz)wave were raised by IL-6, and the Group A and Group C have significant difference compare with the Group B at times of 1h, 4h, 8h, 12h(P＜0.05), but except Group D. The dynamic change of the four groups amplitude of the high-frequency(100Hz)wave, Group A have significant difference compare with the lh at times of 2h, 4h, 12h, 24h (P＜0.05), Group B have significant difference compare with the lh at times of 4h, 8h, 12h (P＜0.05), Group C have significant difference compare with the lh at times of 4h, 24h(P＜0.05), the change of Group D wasn't significant.(4) The change of EEG shape was dynamic in four groups, and the shape of Group D like as Group B. the wave of a andβwas majority in the EEG of Group A, which the range of amplitude was from 20μv tol00μv, and unchanged in 24h(amplitude of wave and frequency), epileptic wave (spike and sharp wave) of Group B appeared abundantly, the majority of that is high frequency (70-200Hz), high amplitude (100-200μv)and paroxysm. Epileptic wave of Group C is sporadic, and compare with Group B, the wave reduced significantly, the frequency and amplitude is low, just likes Group A.2.The effect of IL-6 on expression of rats hippocampal glial fibrillary acidic protein (GAFP) and the role of SSa.In four groups, the expression of GFAP was increased by IL-6, and the Group A and Group C have significant difference compare with the Group B at times of 4h, 8h, 12h, 24h(P＜0.05), but except Group D. And, the change of expression was dynamic. Group A and Group C have significant difference compare with Group B at times of 4h, 8h, 12h, 24h (P＜0.05), The band of GFAP in Group B is thicker than it inGroup A and Group C.Conclusions(1) The sharp wave were induced by IL-6, and IL-6 can raise the power and amplitude of the high-frequency (100Hz) wave. IL-6 can induced epileptic discharge of rats and the effect have relationship with action time that can be confirmed in this study. (2) The increased of GFAP's expression can be induced by IL-6. Astrocyte can be activated by IL-6 in this study confirmed, and then, to affect the occurrence of epilepsy.(3) The high dose of SSa can inhibit the epileptic EEG of rats induced by IL-6. SSa can significantly inhibit the number of the sharp wave and can inhibit the power and amplitude of the high-frequency (100Hz) wave. But in this study, the effect of low-dose of SSa on the EEG wasn't significant, suggested that the effect was dose-dependent. The increased of GFAP's expression can be induced by lateral cerebral ventricle injection of IL-6, SSa can inhibit the expression of GFAP induced by IL-6 in this study. The anti-epileptic effect of SSa that may be inhibit the epileptic electrical activity of brain and astrocyte activated by IL-6.
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