利莫那班对颅脑外伤模型大鼠癫痫易感性的影响

Effect of rimonabant on susceptibility of epilepsy in rat models after head injury

目的:观察利莫那班在大鼠颅脑外伤后不同时期对癫痫易感性的影响,探讨利莫那班能否干预外伤后癫痫的发生。方法:105只大鼠分为模型处理组(45只)、模型组(45只)和空白对照组(15只)。模型处理组和模型组大鼠通过外侧液压打击法制备颅脑外伤模型,并在打击后2min分别腹腔注射利莫那班和生理盐水。上述2组大鼠继续均分为3个不同时间点(每个时间点15只),分别在液压打击后24h、1周和6周时腹腔注射戊四唑,空白对照组大鼠直接腹腔注射戊四唑。观察各组大鼠癫痫发生的潜伏期和出现全身强直阵挛性癫痫(GTCS)大鼠的数量。结果:液压打击后6周时,模型组大鼠癫痫发生的潜伏期较打击后24h时和1周时缩短(F=12.93,P=0.023;F=11.80,P=0.016);模型处理组大鼠癫痫发生的潜伏期在打击后24h时较液压打击后1周时和6周时缩短(F=22.51,P=0.001;F=11.69,P=0.024)。空白对照组大鼠癫痫发生的潜伏期较模型组6周时(F=14.74,P=0.03)和模型处理组24h时(F=18.33,P=0.007)延长;打击后24h时,模型组大鼠癫痫发生的潜伏期较模型处理组延长(t=2.97,P=0.009);打击后6周时,模型组大鼠癫痫发生的潜伏期较模型处理组缩短(t=2.31,P=0.033)。在打击后6周时模型处理组发生GTCS大鼠的数量较模型组减少(χ2=6.67,P=0.033)。结论:利莫那班在脑外伤后急性期时可增加癫痫易感性,而在慢性期时其可降低癫痫易感性。

Objective：To observe the effect of rimonabant on the susceptibility of epilepsy in the rats after head injury,and to explore whether rimonabant can block epilepsy in the rats after head injury.Methods：A total of105 rats were divided into model-management group（n=45）,model group（n=45）,and blank control group（n=15）.The rats in model-management group and modeling group were used to establish the traumatic head injury models by fluid percussion injury（FPI）method,and the rats were intraperitoneally administered with rimonabant and saline 2min after FPI,respectively.The rats in model and model-management groups were intraperitoneally injected with pentylenetetrazole at 24 h,1week,and 6weeks after FPI.The rats in blank control group were also intraperitoneally injected with pentylenetetrazole.The latency of epilepsy and the number of generalized tonic clonic seizures（GTCS）of the rats in each group were observed and compared.Results：In model group,the latency of epilepsy of rats at 6weeks after PFI was obviously shorter than those at 24 hafter FPI（F=12.93,P=0.023）and1week after FPI（F=11.80,P=0.016）.However,in model-management group,the latency of epilepsy of the rats at 24 hafter PFI was shorter than those at 1week after FPI（F=14.69,P=0.024）and 6weeks after FPI（F=11.69,P=0.024）.The latency of epilepsy of the rats in blank control group was longer than those at6 weeks after FPI in model group（F=14.74,P=0.03）and at 24 hafter FPI in model-management group（F=18.33,P=0.007）.The latency of rats in model group at 24 hafter FPI was longer than that at 24 hafter FPI in model-management group（t=2.97,P=0.009）;the latency at 6weeks after FPI in model group was shorter than that at 6weeks after FPI in model-management group（t=2.31,P=0.033）.The number of rats with GTCS in model-management group was decreased at 6weeks after FPI than that in model group（χ2=6.67,P=0.033）.Conclusion：The rimonabant can increase the susceptibility of epilepsy in the acute stage of head injury and plays an opposite role in the chronic stage.