Effect of Huazhuo Jiedu Shugan Prescription on Learning， Memory， and PI3K/Akt/GSK-3β Signaling Pathway in Epileptic Rats / 中国实验方剂学杂志

Objective:To observe the effects of Huazhuo Jiedu Shugan Prescription （HZJDSG） on learning， memory， and the expression of phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt）/glycogen synthase kinase-3<italic>β</italic> （GSK-3<italic>β</italic>） pathway-related proteins in epileptic rats， and to explore its possible mechanism. Method:Forty-eight SPF male SD rats were randomly divided into a normal group， a model group， a sodium valproate （0.19 g·kg^-1） group， and low- （2.7 g·kg^-1）， medium- （5.4 g·kg^-1）， and high-dose （10.8 g·kg^-1） HZJDSG groups， with eight rats in each group. The normal group received 0.9% sodium chloride solution （0.035 g·kg^-1） by intraperitoneal injection， and the other five groups received pentetrazol （PTZ） at the same dose to induce a chronic epilepsy model for a total of 14 times. The drug groups received corresponding drugs and the normal group and the model group received 0.9% sodium chloride solution at the same volume once a day for 28 days. During the drug intervention period， epilepsy was maintained in each modeling group by intraperitoneal injection of PTZ on day 7， 14， 21， and 28. The behavioral changes of rats were observed by Morris water maze and the pathomorphological changes of rat hippocampal neurons by hematoxylin-eosin （HE） staining. The protein expression of phosphorylation Akt（p-Akt）and p-GSK-3<italic>β</italic> was detected by immunohistochemistry and the protein expression of PI3K， Akt， p-Akt， GSK-3<italic>β</italic>， and p-GSK-3<italic>β</italic> by Western blot. Result:Compared with the normal group， the model group showed prolonged platform finding time （<italic>P</italic><0.01）， reduced number of platform crossings （<italic>P</italic><0.01）， structural damage of neurons in the CA1 region of the hippocampus， down-regulated protein expression of p-Akt and p-GSK-3<italic>β </italic>in the CA1 region of the hippocampus （<italic>P</italic><0.05）， and reduced relative expression of PI3K， p-Akt， and p-GSK-3<italic>β</italic> in the hippocampus （<italic>P</italic><0.01）. Compared with the model group， the sodium valproate group and the HZJDSG groups showed shortened platform finding time （<italic>P</italic><0.01） and improved neuronal structure in the CA1 region of the hippocampus， while the sodium valproate group and the high- and medium-dose HZJDSG groups exhibited increased number of platform crossings （<italic>P</italic><0.01）， up-regulated protein expression of p-Akt and p-GSK-3<italic>β</italic> in the CA1 region of the hippocampus （<italic>P</italic><0.05）， and elevated relative expression of PI3K， p-Akt， and p-GSK-3<italic>β</italic> （<italic>P</italic><0.01）. Conclusion:HZJDSG can improve the learning and memory of epileptic rats， and its antiepileptic effect may be achieved by the activation of PI3K/Akt/GSK-3<italic>β</italic> pathway-related proteins.