| BackgroundEpilepsy is a common disease of nervous system, whose course is long and which occurs repeatedly. It is a group of clinical syndromes which are caused by repeated abnormal synchronization synchronous discharge and featured by paroxysmal nature, transience, repeatability and mechanical malfunction of central nervous system. Because epilepsy has the following characteristics, such as paroxysmal nature, transience and repeatability, its long-term and repeated attack not only causes harms for patients’ body but also seriously affects their life quality, leads to a series of spiritual and mental problems and brings heavy burden on families and the society. Factors that epileptics usually have, such as sense of disgrace, social withdrawal, activity limitation, overprotection and aloneness, may affect their life quality. Thus, how to prevent and treat epilepsy correctly and effectively has become a problem that draws much attention of the medical field.According to findings of epidemiological investigations published by WHO in2005, it was shown that there were50million epileptics in the world, whose average yearly morbidity was0.5‰-1‰, and China had over9million epileptics whose morbidity was about23/0.1million/year now. Currently, treatment for epilepsy mainly focuses on taking antiepileptic medicine orally. Although antiepileptic medicine that is used clinically can control about80%of patients’ state of illness and completely remit70%of patients’ states of illness, course of epilepsy is long. In addition, most of antiepileptic medicine has many untoward effects so that toxic and side effect will be generated after taking such medicine for a long time. Besides, price of antiepileptic medicine is high, which brings heavy burden on patients. Traditional TCM (traditional Chinese medicine) therapy for this illness has shown unique advantages and many kinds of medicine, which are used clinically, have good antiepileptic effect and are featured by slow release, long action time, few side effects and light toxic and side effect. TCM pair is usually used as core of medicine and applied to clinical treatment. By studying compatibility of TCM pair, this task explored its anti-epileptic mechanism in order that it could provide reliable experimental basis for anti-epileptic treatment by TCM.Epilepsy belongs to scope of TCM ’epilepsy disease’. Pathogenesis of epilepsy disease has close relationship with liver dysfunction. Generation of wind, phlegm and stasis is pathological changes in liver dysfunction and unblocked nature, so treating liver is a key to treatment of epilepsy. Fuxin Xiong a modern famous veteran doctor and Professor Baotian Chen especially advocate that treatment of epilepsy should start with liver and center on using radix bupleuri compound to treat epilepsy. The medicine pair of radix bupleuri and Radix Paeoniae Alba usually utilizes compatibility to sooth and nourish the liver. Radix bupleuri can sooth liver-qi stagnation and enhance Yang, whose effective element saikoside can enhance immunity and has anti-inflammatory and anti-convulsion effect. Besides, Radix Paeoniae Alba can nourish blood and liver as well as stabilize liver Yang, whose effective constituent albiflorin as effect of analgesia, calming and anti-convulsion. In the aspect of clinical epileptic treatment, application of compatibility of radix bupleuri and Radix Paeoniae Alba has obvious curative effect. However, there are few literatures and reports related to which proportion of radix bupleuri and Radix Paeoniae Alba in compatibility should be applied to clinical treatment can achieve the best curative effect on epileptic treatment.There are various types of epileptic seizure and its pathogenesis is complicated. Thus, it has been one of hot spots of neuroscience researches to build laboratory animal epilepsy models that can simulate people’s epileptic seizure with help of experimental animals and discuss pathogenesis of epilepsy so far. Currently, models about epileptic seizure, which have been accepted in the whole world, include MES mode, PTZ mode, in Strychnine model and in Pilocarpine model etc. For epilepsy models with different sites of action and modes of action, mechanisms of their antiepileptic medicine are different. This research group observed impacts of application of compatibility between radix bupleuri and Radix Paeoniae Alba on epileptic seizure of mice with experimental convulsion.PurposeThis experiment was started with the situation that epileptic treatment should begin with liver and figured out the optimum compatibility ratio between radix bupleuri and Radix Paeoniae Alba for anti-experimental epilepsy by observing impacts of radix bupleuri and Radix Paeoniae Alba in different compatibility ratios on epileptic seizure of mice with experimental convulsion in order to guide TCM epileptic therapy in clinical treatment. At the same time, it discussed possible function channels and mechanisms that application of the compatibility between radix bupleuri and Radix Paeoniae Alba on epileptic seizure of mice with experimental convulsion had, providing experimental basis for the TCM theory that epileptic treatment should begin with liver.Methods1. The maximal electroshock seizure mice modelSeventy qualified Kunming male mice selected by screening were randomly divided into seven groups:the model group(A),the positive control group(B), RB-PA2:lgroup(C),RB-PA1:1group(D),RBgroup(E),PAgroup(F),RB-PA1:2group(G). The positive control group received the administration of phenytoin0.025g.kg-1, the dosage of Radix Bupluri and Radix Paeoniae Alba in Different Compatibility Proportion were10.4g.kg-1, while the model group the equal volume of physiological saline. Each group received continious lavage administration for7days,twice a day. MES experiment is advanced60minutes after the last administration by using experimental spectrometer (YSD-4G) of pharmacological and physiological in a single stimulation way, stimulation parameter for100V,2Hz, tonic hind limb extension was considered as convulsions target, the number of convulsions,the duration of tonic hind limb extension and convulsions rate would be recorded and calculated.2. Epilepsy of mice model induced by PentylenetetrazoleSeventiy qualified Kunming male mice were randomly divided into seven groups:the model group(A), the positive control group(B), RB-PA2:1group(C),RB group(E), PA group(F), RB-PA1:2group(G). The positive control group received the administration of diazepam0.004g.kg-l,the dosage of Radix Bupluri and Radix Paeoniae Alba in Different Compatibility Proportion were10.4g.kg-1, while the model group the equal volume of physiological saline. After the continious lavage administration for7days, twice a day.60minutes after the last administration,each group receivd the administeration of85mg/kg PTZ, then they were observed for30minutes of latency to the first convulsion, percentage of animals exhibiting convulsions, latency to death, and percentage of deaths.3. Epilepsy of mice model induced by Strychnine (STR)Grouping and administration is similar to the model induced by Pentylenetetrazole.60minutes after the last administration,each group receivd the administeration of2mg/kg Strychnine,then they were observed for15minutes of latency to the first convulsion, latency to death, and percentage of deaths.4. Pilocarpine-induced seizures testGrouping and administration is similar to the model induced by Pentylenetetrazole.60minutes after the last administration,each group receivd the administeration of400mg/kg pilocarpine,then they were observed for15minutes of latency to the first convulsion, latency to death, and percentage of deaths.5. Statistical analysisThe data were statistically analyzed by using SPSS13.0software, One-Way ANOVA was applied to the compare of mean among several samples, Tukey was used if multiple comparision among groups was in keeping with homogeneity of variance,if not, Dunnett would be applied,chi-square test was utilized in the comparision of enumeration data and rate. The value of P<0.05was considered statistically significant.Result1. The effect of different proportion of RB-PA on the epilepsy induced by MESCompared with group A,other groups could result in inhibiting the incidence of tonic hindlimb extension in mice induced by MES,while group C and D have significant differences.2. The effect of the different proportion of RB-PA on the epilepsy induced by PTZCompared with group A, Group B,C,D and G could extend the onset of clonic latency of seizure in mice induced by PTZ significantly(P<0.05), especially in Group B and C (P<0.01); Group B,C and D could extend the onset of latency of seizure significantly (P<0.05);and in the comparison of latency of dean, Group B and C have significant differences (P>0.05)3. The effect of the different proportion of RB-PA on the epilepsy induced by STRCompared with group A, Group B can extend the onset of latency of seizure and the latency of dean (P<0.05),while other groups have no significant differences (P>0.05)4. The effect of the different proportion of RB-PA on the epilepsy induced by PLCPCompared with group A, Group B can extend the onset of latency of seizure (P<0.05),while other groups have no significant differences (P>0.05). Group B,C,D,E and G could extend the onset of latency of dean in mice induced by PLCP significantly (P<0.05), especially in Group B (P<0.01)Conclusion1. Acute epilepsy model which is induced by maximal electroshock convulsions, pentylenetetrazol,strychnine and pilocarpine is successfully established, the technology of model of establishment is mature, the operation is relatively simple, it has a higher success rate and a certain representation.2. Application of the compatibility between radix bupleuri and Radix Paeoniae Alba had anti-convulsion effect on the model related to mice’s acute epilepsy caused by maximum electro-convulsion, pentrolone and pilocarpine. However, its anti-convulsion effect was weaker than that of diazepam or dilantin.3. Application of the compatibility between radix bupleuri and Radix Paeoniae Alba had good anti-convulsion effect and its anti-convulsion effect was better than that of single radix bupleuri or Radix Paeoniae Alba. The compatibility ratio of radix bupleuri to Radix Paeoniae Alba, i.e.,2:1, had the best anti-convulsion effect. |