| BackgroundEpilepsy, a functional disturbance of the CNS and induced by abnormal electrical discharge manifests by recurrent seizure. The morbidity rate in developed countries is relatively lower than in developing countries. Epidemiological data shows that nearly9million Chinese people with epilepsy, symptomatic epilepsy in the majority. According to the epidemiology statistics, at present the incidence of epilepsy patients is approximately300,000to400,000every year in China. In a word, the number of patients suffer from epilepsy in our country is enormous. Compared to these,50%or more patients in the country can not be treated normally. Furthermore, its prominent clinical characteristic has the unpredictability, which repeatedly paroxysmal and each time manifests suddenly andaffected epilepsy sickness patient’s life, the work and social interaction ability enormously, reduced patients’quality of life. Treating epilepsy patient is a difficult and important mission.At present we controlled epilepsy primarily still by chemistry medicine, commonly used antiepileptic which could control70%～80%epilepsy patient to manifest suddenly epileptic seizuresuch as the Diphenylhydantoin, the Valproic Acid, the Carbamazepine and so on. But the pharmacokinetics effects and the side effect, such as fetal malformations, cognitive effects and bone density effectual limited their application. Compared with traditional chemical medicine, some new antiepileptic drugs, such as Gabapentin, Lamotrigine and Oxcarbazepine, which is degraded the drug tolerance. But because of the expensive price, the application is limited. About25%of epilepsy patients tolerance of various therapies, including antiepileptic drugs, epilepsy surgery, vagus nerve stimulation. This requires the development of new antiepileptic drugs. Previous studies have shown that the antiepileptic effect of traditional Chinese medicine through the regulation of neurotransmitter,regulation of ion channels,inhibit the proliferation of glial cells, free radical scavenging.Er-shi-wu-wei Coral Pill is a traditional Tibetan medicine, which has the effect of clearing heat, promoting blood circulation,relieving pain, and so on. This drug can treat with white vein disease, whose Symptoms include confusion, numbness, dizziness, pain in brain, blood pressure is not adjusted, headache, epilepsy and all kinds of neuropathic pain. Previous clinical studies have shown that the binding of AEDs treatment of symptomatic epilepsy, particularly refractory epilepsy achieve good results. This drug blinding of AEDs not only can improve the efficacy of AEDs but also reduce the incidence of the adverse events. But how does the antiepileptic effect of the single drug(Er-shi-wu-wei Coral Pill)? and which type of epilepsy seizure is the most effective? the current study is still in a blank state.The traditional Chinese medicine hasthe good anti-epilepsy function, but its mechanism is not often explicit, obtaining from the single taste traditional Chinese medicine active constituent to study not only can be clear about the anti-epilepsy mechanism, but also advantageous to promote modernization of traditional chinese medicine.The pentetrazole(PTZ) convulsion model and the MES model are epilepsia major model used mostly and study transparently. It is clear that the drug which can prevent the epilepsia major made from the above animal models, can treat the epilepsia major patients in clinic.Method and content1. Making the cute PTZ convulsion rat model60of wistar rats were divided into6groups, A, B, C, D, E, and F group, and there were10rats in each group. All of rats in each group were administered by intragastric administration7days at8:00am and20:00pm. The group of A was given equal volume of water, while the E was given VPA by200mg/(kg.d), and the B、C、D are given Er-shi-wu-wei coral pill by different concentration, such100mg/(kg-d) and200mg/(kg·d) and400mg/(kg·d). The group of F Was given VPA by200mg/(kg.d) firstly and Er-shi-wu-wei coral pill by100mg/(kg-d)8hours later. After1hour of the above administrations, all groups of rats were injected PTZ by peritoneal, according to50mg/kg. And then observed the ethology change of the rats immediately in30mins, recording the incubative stage of clonus and the number of rats in each group in different stroke grade.2. Embedding electrode and recording the EEG18of wistar rats, was divided into6groups evenly. All of rats in each group were administered by intragastric administration7days at8:00am and20:00pm.The group of A was given equal volume of water, while the E was given VPA by200mg/(kg.d), and the B、C、D are given Er-shi-wu-wei coral pill by different concentration, such100mg/(kg-d) and200mg/(kg-d) and400mg/(kg-d). The group of F Was given VPA by200mg/(kg.d) firstly and Er-shi-wu-wei coral pill by100mg/ (kg-d)8hours later. After3days every group of rats were anesthetized by10%chloral hydrate, according to350mg/kg, then fixed stainless steel electrode in hippocampus and cortex frontal lobe, thereby fixed by dental base acrylic resin powder and dentistry Portland cement, then sutured scalp. One week later, recorded The EEG until5mins.3. Making the MES model.Bolting sixty fit mouse according pharmacological multi-functional implement, and then dividing into6groups, The group of A was given equal volume of water, while the group of E was given VPA by400mg/(kg.d), and the B、C、D are given Er-shi-wu-wei coral pill by different concentration, such200mg/(kg-d) and400mg/(kg-d) and800mg/(kg-d). The group of F Was given VPA by400mg/(kg.d) firstly and Er-shi-wu-wei coral pill by200mg/(kg-d)8hours later. After1hour of the above administrations, all groups of rats were injected PTZ by peritoneal, according to50mg/kg. And then observed the ethology change of the rats immediately in30mins, recording the incubative stage of clonus and the number of rats in each group in different stroke grade. Atterl hours of the last administration, giving electric stimulation.Result1. The effect of different groups on seizure incubation period and grade in PTZ acute convulsion model.The incubation period of PTZ acute convulsion could increase in the group of A, B, C, D, E, F(F=4.698, P=0.001), but the group of B, C, D, E and F has no statistical difference. The three groups of Er-shi-wu-wei coral pill did not had dose-effect relationship.2. the EEG of different groups in PTZ acute convulsion model.The EEG in group of Al (normal group) was base wave, such asα, β wave, and scatered θ wave, and had no obvious rhythm. The EEG in group of A2had a large number of high amplitude sharp waves, spikes, spike-slow wave. The epileptic discharges in group of C、D and F were inhibited, and there was only a very small number of spikes or sharp waves. The EEG in group of B had more sharp waves spikes, spike-slow wave, but the amplitude was lower than the model group(A2). The EEG in group of E had scattered spikes or sharp waves and low amplitude.3. The effect of different groups in MES mouse model.The convulsion rate in differernt groups was statistically significant (χ2=29.000, P=0.000),The convulsion rate in group of B, C, D, E and F was lower than in thegroup of A. The convulsion rate in group of F was the lowest, and convulsion rate in the group of E was lower than in the group of D, C, B group. And the group of D, C, B did not have close dose-effect relationship.Conclusion1. Three Ershiwuweishanhu coral pills compatibility program(the three groups of Ershiwuwei coral pill adding-on therapy) are significantly reduce the seizure frequency of symptomatic epilepsy, to reduce the degree of epileptic discharge, improving the degree of headache and cognitive impairment.2. Both Er-shi-wu-wei coral pill and VPA have the effect of antiepilepsy on PTZ seizures in rats, MES seizures in mice.3. All the doses of Er-shi-wu-wei coral pill had action of Analgesic.4. All the doses of Er-shi-wu-wei coral pill had action of sedation. |
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