Study On Synergistic Effect Of Wuling Capsule On Sodium Valproate In The Treatment Of Epileptic Rats

ObjectiveThe pentylenetetrazol and kainate induced respectively the epilepsy rats model by Wuling capsule and sodium valproate alone and combined treatment,investigation on the EEG of epileptic rats and the effect on seizures,studying the influence on the ability of learning and memory of epileptic rats,studying the impact of liver in the epilepsy rats by HE staining and serum liver function tests.Furthermore,investigating the effect of Wuling Capsule on the plasma pharmacokinetics of sodium valproate in epileptic rats.Methods1.To investigate the EEG of epileptic rats and the effect on seizures :80 SD male rats were randomly divided into two groups,namely the kainic acid epilepsy group and the pentylenetetrazol epilepsy group.The two epileptic groups were randomly divided into 5 groups,saline group,model group,valproate group,Wuling capsule group and sodium valproate combined with Wuling capsule group.Saline group of the pentylenetetrazol epilepsy group was injected with saline,the other groups were intraperitoneally injected with pentylenetetrazol solution.Saline group of the kainate epilepsy group was injected with saline,the other groups were injected with kainic acid in hippocampus.Saline group and model group were given saline,and the other groups were given the corresponding drugs.the pentylenetetrazol epilepsy group was given the corresponding drugs for 1 h later,injection of pentylenetetrazol solution everyday,consecutive 28 d,stop injection of pentylenetetrazol solution and continue to give drugs,7 d later,injection of pentylenetetrazol solution,recording the EEG of epileptic rats.The kainic acid epileptic group was injected with kainic acid and given the corresponding drugs for 15 d,recording the EEG of epileptic rats,and continued to be given the corresponding drugs for 60 d,recording the seizures.2.2.To investigate the influence on the ability of learning and memory of epileptic rats : according to the above modeling methods to establish the rats model of epilepsy,the above-mentioned two epileptic groups were given the water maze testing on 45 d and 90 d,recording the escape latency and the number of crossing platform.3.To investigate the impact of liver epilepsy in the epilepsy rats : according to the above modeling methods to establish the rats model of epilepsy,the two epileptic rats groups were randomly divided into saline group,model group,sodium valproate group and sodium valproate combined with Wuling capsule group,5 rats in each group,every group was given drugs for 90 d,then the epileptic rats were anesthetized,blooded from orbital cavity and removed the liver,testing content of ALT,AST,r-GT and ALP through the automatic biochemical analyzer and observing changes of the liver by HE staining.4.To study the effect of Wuling Capsule on the plasma pharmacokinetics of sodium valproate in epileptic rats: according to the above modeling methods to establish the rats model of epilepsy,the two epileptic rats groups were randomly divided into sodium valproate group,sodium valproate combined with Wuling capsule group,6 rats in each group.The rats in the combined group were given Wuling capsule for 7 d and given Wuling capsule and sodium valproate tomorrow,the sodium valproate group was given sodium valproate.blood was collected at certain time points,the concentration of sodium valproate in plasma was determined.The pharmacokinetic parameters of sodium valproate were analyzed by DAS3.0 software,and the time curve was drawn.Results1.In the model of epilepsy induced by kainic acid,sodium valproate combined with Wuling capsule group could inhibit the seizures,significantly reduces the level and frequency of seizures,the effect is better than sodium valproate and Wuling capsule group.The results of EEG test show that the combination of drug group can significantly reduce the amplitude and frequency of EEG of epileptic rats,and the effect is better than that of Western medicine and traditional Chinese medicine group.2.In place navigation test,comparing with the model group,the latency of the rats in the valproate group was decreased,there was a significant difference on the 45 d and there was no significant difference on the 90 d,while the latency in the Wuling capsule group and the combined group was significantly lower than that in the model group.In the space exploration test,comparing with the model group,the sodium valproate group rats had no significant difference in the number of cross platform,the Wuling capsule group significantly increased the number of cross platform;the combined group had increased significantly in the number of crossing platform,but significantly higher than sodium valproate group.The improvement of learning ability of rats in Wuling capsule group and combined group is better than that in sodium valproate group3.HE staining results showed that liver cells in rats with sodium valproate was fused with others,liver cells had unclear boundaries and severe edema and fatty degeneration.Inflammatory response of liver cells was significantly reduced in rats with sodium valproate combined with Wuling capsule,the number of liver cells was significantly reduced and edema and fatty degeneration were significantly reduced.Serum liver function tests showed that Wuling capsule could significantly reduce the content of ALP in serum of rats that were damaged liver by sodium valproate VPA.The content of ALT,AST and r-GT in serum of rats have no significant difference,but the content of ALT and AST were reduced.It shows that the combined group can improve the liver injury of epilepsy rats induced by sodium valproate.4.Compared with sodium valproate group,AUC(0-480min)and Cmax in combined group were significantly increased,and CLz/F was significantly decreased.There was no significant difference in T1/2z,Tmax and MRT(0-480min)in the combined group,but they all extend.ConclusionWuling capsule combined with sodium valproate could better restrain epileptic seizures induced by kainic acid and pentylenetetrazol and improve the ability of learning and memory of epileptic rats.The combined group can improve the liver injury of epileptic rats induced by sodium valproate and effect the concentration of sodium valproate in plasma in epileptic rats.