Tripterygium Wilfordii Polyglycoside: Effects On The Learning And Memory Of Rats With Epileptisy And The Expression Of Neurogranin And Protein Kinase C

Objective: To investigate the roles of Tripterygium Wilfordii Polyglycoside (TWP) in the learning and memory of rats having epileptisy induced by pentylenetetrazole (PTZ) and the effects of Neurogranin (Ng) and protein kinase C (PKC) expression and to explore the possible association among TWP, PTZ, and epileptisy.Methods: A total of 90 rats, with normal learning and memory ability, selected using Morris water maze and Y maze, were randomly invided into four groups: 3 epileptisy model groups (PTZ Group, TWP1 Group, and TWP2 Group) and one normal saline group (NC Group). Epileptisy model was produced through injecting PTZ (35mg/kg?d) into the peritoneal cavity of rats during the 1st to 28th day of the treatment. Exception for the administration of PTZ, rats from TWP1 and TWP2 Group repectively received the intragastric administration of 10 mM/kg?d and 30 mM/kg?d TWP (contained in carboxymethylcellulose sodium) within 30 min before the administration of PTZ. While these from NC Group only accepted the treatment of normal saline at the same dose and method to PTZ. During the 29th to 35th day, all rats were examined through Morris water maze and Y maze test and their learning and memory abiligy was evaluated according to Racine criterion, then their hippocampuses were separated to analyze the the expression levels, including mRNA and protein, of Ng and PKC gene by means of real-time quantitative PCR (RT-qPCR) technique and enzyme-linked immunosorbent assay (ELISA) method, repectively, on the 36th day.Results: We found the rats from the groups of TWP treatment (TWP Group, consisting of TWP1 and TWP2 Group) showed shorter running time (PTZ vs TWP1 Group, 40.6 s/28.8 s; PTZ vs TWP2 Group, 40.6 s/30.0 s, P < 0.05) and higher right rate (PTZ vs TWP1 Group, 45.0%/66.8%; PTZ vs TWP2 Group, 45.0%/67.0%, P < 0.05) compared to PTZ Group through Morris water maze test, similar to NC Group (P > 0.05); while there was not significant difference among four groups in escape latency (P > 0.05). Y maze test exhibited that rats from TWP Group (3.50 and 3.17 for TWP1 and TWP2, respectively), compared with those from PTZ Group (5.17), had decreased frequency of incorrect response with < 0.05-P value, which resembled that of rats from NC Group with (P > 0.05). The total reaction time, however, had not statistically significant difference among four groups (P > 0.05). In the analysis of the expression of Ng and PKC gene by RT-qPCR and ELISA, we furthermore found that the levels of Ng and PKC expression, including mRNA (increased 50%-70%) and corresponding protein levels (increased 1.5 to 1.7 times), were higher in the TWP Group than in the PTZ Group (P < 0.05), resembling the values of NC Group with > 0.05-P value. However, we did not find the difference among TWP1 and TWP2 Group in the expression levels of these genes (P > 0.05).Conclusion: These results suggested that TWP might be able to effectveily improve the learning and memory abiligy of rats featuring epileptisy, possibly correlated with the up-regulation of Ng and PKC gene in the hippocampuse tissues.