摘要
目的:观察托吡酯(TPM)对戊四氮点燃大鼠海马生长相关蛋白-43(GAP-43)蛋白和mRNA表达的影响。方法:健康成年雄性SD大鼠40只,随机分为4组,每组10只。模型对照组大鼠灌胃给予生理盐水(10mL/kg),低、高剂量TPM组分别按40mg/kg和100mg/kg给予10g/LTPM生理盐水溶液,空白对照组给予等量生理盐水,1h后,前3组大鼠腹腔注射10g/L戊四氮(35mg/kg)建立戊四氮点燃大鼠癫模型,空白对照组给予等量生理盐水。当模型对照组大鼠行为达到点燃时,应用RT-PCR方法半定量检测GAP-43mRNA的表达,应用免疫组织化学方法检测齿状回、海马CA3区和CA1区内GAP-43蛋白的表达强度。结果:与空白对照组相比,模型对照组,低剂量TPM组和高剂量TPM组大鼠齿状回与CA3区的GAP-43mRNA和蛋白表达强度升高(P<0.05);与模型对照组相比,低剂量TPM组和高剂量TPM组大鼠齿状回和CA3区的GAP-43mRNA和蛋白表达强度降低(P<0.05)。结论:戊四氮点燃大鼠海马GAP-43表达增强,表明突触重建参与了癫发生的病理过程。TPM可抑制GAP-43的过表达,2种剂量的抑制作用无差异。
Aim -To observe the effects of topiramate （TPM） on the mRNA and protein expression of growth associated protein-43 （GAP-43） in the hippocampus of pentylenetetrazole （PTZ） -kindled rats. Methods： Forty adult male SD rats were randomly divided into 4 groups（ n = 10）. The rats of model group were given normal saline at 10 mL/kg by garage ; the rats of low TPM group and high TPM group were given 10 g/L TPM at 40 mg/kg and 100 mg/kg,respectively by garage;the rats of control group were given the same amount of normal saline as other groups daily. After 1 h,the rats in first 3 groups were given PTZ to build up epilepsy model, and the rats in control group were given the same amount of normal saline. When the spasm of rats in the first 3 groups reached kindling,the expression of GAP-43 mRNA and protein in the dentate gyrus （DG） , CA1, CA3 regions of hippocampus were detected by RT-PCR and immunohistochemistry, respectively. Results： Compared with control group,the expression level of GAP-43 mRNA and protein in model group,low TPM group and high TPM group were higher（ P 〈 0.05） ;compared with model group,the expression level of GAP-43 mRNA and protein in low TPM group and high TPM group were lower （ P 〈 0.05）. Conclusion ： The increased GAP-43 expression in the hippocam- pus of the rats after PTZ injection indicates the changes in the neuronal plasticity are probably related to forming the abnormal discharge circuit, and finally inducing the seizures in rats. TPM can prevent the GAP-43 overexpression in the hippocampus of the PTZ-induced epilepsy rats,and the inhibitory action is not related to the dose.
出处
《郑州大学学报（医学版）》
CAS
北大核心
2008年第5期888-892,共5页
Journal of Zhengzhou University(Medical Sciences)
基金
河南省科技攻关基金资助项目0124170634
郑州大学中青年骨干教师资助项目2002年
郑州大学第一附属医院博士启动项目
郑州市科技局资助项目064SGD33218-20
关键词
癫痫
戊四氮
大鼠
生长相关蛋白-43
托吡酯
epilepsy
pentyenetrazol
rat
growth-associated protein-43
topiramate
