| ObjectivesStudy the carbamazepine combined with Naoxintong and Naoxinqing therapy,observing of seizure stage and frenquency in the chronic epileptic rats model induced by Kainic acid,discussing the effect of the carbamazepine combined with Naoxintong and Naoxinqing on behavior,hippocampus neuron,antioxidant index and Bcl-2/Bax ratio of the chronic epileptic rats.Exploring the effecting of Naoxintong and Naoxinqing on the pharmacokinetics and brian tissue distribution of carbamazepine.Methods1.The SD rats were divided into 7 groups,saline group,model group,carbamazepine group,carbamazepine combined Naoxintong group,Naoxintong group,carbamazepine combined Naoxinqing group,Naoxinqing group.The saline group were given saline,the other groups were injection of Kainic acid in intracerebroventricularly.After making the model successfully,in addition to the saline group and model group were given saline,the other groups were given the corresponding drugs,the seizure stages and frenquency were observed.2.The Water maze and Eight arm maze training were performed at the 7 groups rats were fed drug for two months,the exploration of Water maze time and the number of crossing the plat form were recorded,reference memory errors、working memory errors and the total time of eating food in the Eight-arm radial maze were recorded.3.21 rats were selected randomly into 7 groups of three,after Water maze and Eight arm maze test,the rats of each groups were narcosised by 10% chloral hydrate intraperitoneal.The pathology of the hippocampal were observed by HE and Nissl staining.4.54 rats were selected randomly from SD nomal rats,SD epilepsy rats after first giving drug and long-term administration into 3 groups of eighteen.18 rats were divided into 3 groups,carbamazepine group,carbamazepine combined Naoxintong group,carbamazepine combined Naoxinqing group,blood and brain tissue samples were collected at different time,the concentrations of carbamazepine in the plasma and brian tissue of rats were detected by HPLC,the pharmacokinetic parameters were calculated using DAS2.0.5.7 groups rats were fed drug for two months,blood from eye socket and hippocampal were used to examine indexes of antioxidation.6.35 rats were selected randomly into 7 groups of five,Western Blot was used to detect the expression of Bcl-2、Bax in hippocampal.Results1.In the model of epilepsy induced by kainic acid,two combined groups can suppress epileptic seizures,significantly reduced seizure stage and frenquency of epileptic seizures,comparing with carbamazepine group,two combined groups was more effective,two kinds of traditional Chinese medicine groups had no significant effect(P>0.05)on the seizure stage.2.In Water maze test,comparison of time used for positioning navigation,the Place navigation time of each group was gradually reduced,two combined groups and Naoxinqing group compared with the model group,the time was significantly decreased(P<0.01),Naoxintong group was no significant diffenrence.The treatment groups compared with the model group,through the number of effective platform was significantly increased,the other groups were better than carbamazepine group.In Eight arm maze test,the treatment groups compared with the model group,the error of reference memory and working memory were significantly reduced,the other groups were better than carbamazepine group.The treatment groups compared with the model group,the total time of rats ate food was significantly reduced,the other groups compared with carbamazepine group was no significant diffenrence.3.Two combined groups and two kinds of traditional Chinese medicine can improve the damage of neurons and increase the number of neurons in hippocampal CA3 area compared with the model group,carbamazepine combined Naoxinqing group had a significant increase in the number of neurons in hippocampal CA3 area compared with carbamazepine group,other groups were no significant diffenrence.4.Two kinds of traditional Chinese medicine for the first time and long-term lavage in epileptic rats plasma drug had different influence on pharmacokinetic of carbamazepine,the first drug lavage in normal rats plasma,carbamazepine combined Naoxintong group T1/2z(h)and Tmax(h)significantly decreased P<0.05,Cmax(mg/L)significantly increased P<0.05,carbamazepine combined Naoxinqing group AUC(0-480min)(mg/L*h),T1/2z(h)and Tmax(h)significantly decreased(P<0.05),CLz/F(L/h/kg)significantly increased P<0.05,compared with carbamazepine group.Two kinds of traditional Chinese medicine for the first time in saline and epileptic rats brain tissue had no influence on concentration of carbamazepine,the long-term lavage in brain tissue of epileptic rats,carbamazepine concentration of two combined groups werehigher than carbamazepine group in each time point and combined Naoxintong group were more obvious.5.Compared with the model group,T-SOD,CAT and GSH-PX significantly increased,but MDA significantly decreased in serum and hippocampal tissue homogenate of each treatment groups,combined groups and The traditional Chinese medicine groups were more effective compared with carbamazepine group in serum,combined groups was more effective compared with carbamazepine group in hippocampal tissue homogenate.6.Western Blot to detect the ratio of Bcl-2/Bax in the hippocampus of rats in each group,carbamazepine group and two combined groups had significant difference,The traditional Chinese medicine groups had no obvious effect.ConclusionsFrom the experimentation result,two combined groups can suppress epileptic seizures and improve learning and memory function of epileptic rats,enhanced the antioxidant ability and inhibited hippocampal neuron apoptosis of epileptic rats,the mechanism of combined treatment of epilepsy may be related to anti-oxidative stress and anti-apoptosis.Two kinds of traditional Chinese medicine for the first time and long-term lavage in epileptic rats plasma drug had no influence on pharmacokinetic of carbamazepine,the long-term drug epilepsy rats had significant effect on the concentration of carbamazepine in brain tissue,increased the concentration of carbamazepine in the brain of epileptic rats. |
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