妥泰对红藻氨酸致痫大鼠模型海马和颞叶皮层神经细胞caspase-3表达的影响

Effect of Topiramate on the expression of caspase-3 in hippocampus and temporal lobe cortex of rats with seizures induced by kainic acid

目的观察红藻氨酸(KA)的致痫作用并探讨妥泰(TPM)对KA致痫大鼠模型海马和颞叶皮层caspase-3表达的影响。方法取21～30日龄SD大鼠60只,随机分为3组:对照组、模型组和观察组,每组20只。对照组给予生理盐水;模型组仪用KA制作癫痫模型;观察组用KA制作癫痫模型后,加用TPM治疗。观察癫痫大鼠的行为表现、脑电图表现和病理学表现。用免疫组织化学法显示各组大鼠脑切片海马和颞叶皮层caspase-3表达的变化,并用HPIAS-2000显微图像定量分析系统进行图像分析。结果致痫大鼠的行为、脑电图和病理学改变符合癫痫的典型表现。对照组海马和颞叶皮层内存在少量caspase-3基础表达,模型组和观察组注射TPM 6 h后可见海马和颞叶皮层有少量棕褐色caspase-3阳性神经元,3 d时明显增多并达到高峰。与对照组比较,模型组和观察组相同时间点海马和颞叶皮层caspase-3阳性细胞计数均增多(P<0.05),观察组海马和颞叶皮层caspase-3阳性神经元计数与模型组相同时间点比较均减少,差异有统计学意义(P<0.05)。模型组和观察组海马和颞叶皮层caspase-3阳性神经元平均光密度值测定结果显示各相同时间点与对照组相比较所得数值显著增高,且有统计学意义(P<0.05),观察组海马和颞叶皮层caspase-3阳性神经无平均光密度值低于模型组(P<0.05)。结论KA的致痫作用很强,妥泰能抑制癫痫大鼠海马和颢叶皮层caspase-3表达,对癫痫发作大鼠具有神经细胞保护作用。

Objective To obverse the effect of the epileptic function of kainic acid（KA） and（？）o explore the effect of Topiramate（TPM） on the expression of caspase-3 in hippocampus and temporal lobe cortex in epileptic rats model.Methods Sixty cases SD rats aged from 21 to 30 days were randomly divided into three groups：control group（n= 20）,model group（n = 20） and observation group（n =20）.Normal saline were treated in the control group;KA were used to make the epileptic model in the model group and the observation group,after which TPM were added in the observation group.The behavior performance, the electroencephalogram and the pathological section of epilepsy rats were observed.The expression of caspase-3 in hippocampus and temporal lobe cortex of rats were indicated by immunohistochemical method and the images were analysed by HPIAS-2000. Results The behavior,the electroencephalogram and the pathological section of rats epilepted by KA were corresponded with the typical performance with epilepsy.Some expression of casepase-3 were detected in hippocampus and temporal lobe cortex of rats in control group;A few brown caspase-3 positive neurons were found in hippocampus and temporal lobe cortex of rats 6 hours after the injection of TPM in the model and the observation group,with the peak at the third day.The caspase-3 positive counting in the hippocampus and temporal lobe cortex at the same time points in the model group and the observation group were higher than that in the control group（P0.05）.In the observation group the caspase-3 positive counting in the hippocampus and temporal lobe cortex became lower than that in the model group,the difference is of statistical significance（P0.05）.The result of the average optical density titer of the caspase-3 positive neuron in hippocampus and temporal lobe cortex in the model group and the observation group showed that the titer became obviously higher at the same time points than that in the control group,and there was statistical significance（P0.05）.Compared with the model group,the expression of caspase-3 of hippocampus and temporal lobe cortex was obviously lower at the same time points in the observation group（P0.05 ）.Conclusion Effect of the epileptic function of KA is evident.TPM can inhibit the expression of caspase-3 in hippocampus and temporal lobe cortex of epileptic rats, and can protect nerve cells from damage of epileptic seizure.