【Animal modeling】-Effect of lamotrigine on the expression of PGP, MVP and amino acid content in the hippocampus of chronic epilepsy rats

  Objective: To investigate the effect of lamotrigine on the expression and amino acid content of P-glycoprotein and main vault protein in the hippocampus of chronic epilepsy rats.

  Methods: SPF male SD rats were prepared with pentylenetetrazol to prepare chronic epilepsy rats and randomly divided into model group, lamotrigine low-dose (5 mg/kg) group and lamotrigine high-dose (10 mg/kg) group, The healthy rats were taken as the control group, with 15 rats in each group. All groups were intragastrically administered, and the model group and the control group were intragastrically administered with normal saline, and the administration volume was 1 mL/100g. All rats were recorded before and after treatment. The behavioral characteristics and body weight were recorded, the seizure time and brain waves after treatment were recorded, the expressions of PGP and MVP in the hippocampus were detected by immunohistochemistry and Western blot, and the aspartate (Asp) in the hippocampus was detected by HPLC. , Glutamate (Glu) and Glycine (Gly) content.

  Results: The activities of the rats in the control group were normal. The rats in the chronic epilepsy model group showed decreased activity, chewing, rhythmic nodding, head and neck elevation, forelimb clonic seizures, and a few rats erected their tails or clapped their tails on the ground. Lamotrigine group Rats gradually transitioned from head-neck uplifting and forelimb clonic seizures to twitching of erect hair and mouth and facial muscles in the early stage, with rare tail erection or tail-beating. Before treatment, compared with the control group, the model group and lamotrigine The body weight of the two groups were significantly decreased (P<0.05). After treatment, compared with the control group, the body weight, EEG frequency, hippocampal Gly of the model group were significantly decreased (P<0.05), seizure time and EEG amplitude were significantly decreased (P<0.05). 、Asp, Glu, PGP and MVP in hippocampus were increased (P<0.05), compared with model group, body weight, EEG frequency, Gly in hippocampus were significantly increased in lamotrigine group (P<0.05), epileptic seizures were significantly increased (P<0.05). Time, EEG amplitude, Asp, Glu, PGP and MVP in hippocampus were decreased (P<0.05), and showed a dose-dependent trend of lamotrigine.

  Conclusion: Lamotrigine treatment of chronic epilepsy is associated with the reduction of hippocampal PGP and MVP protein and the improvement of hippocampal amino acids.