托吡酯对慢性癫癎大鼠海马碱性成纤维细胞生长因子表达的影响

Effect of Topiramate on the basic fibroblast growth factor expression in hippocampus of a chronic epileptic rat

目的研究托吡酯(TPM)对慢性癫癎大鼠海马碱性成纤维细胞生长因子(bFGF)表达的影响。方法制作戊四氮(PTZ)慢性癫癎点燃大鼠模型,分为PTZ组、TPM组及正常对照组,每组又以5d、10d、15d3个时间点各分为3小组。免疫组化法观察各组海马CA1、CA3区及齿状回bFGF表达,HE染色观察病理形态学改变。结果(1)行为学观察:PTZ组和TPM组在癫癎发作上无明显差别。(2)bFGF表达:①各组齿状回区bFGF表达:PTZ组和TPM组各时点表达不断增高,与正常对照组比较差异有统计学意义(均P<0.01),尤以10d及15d时增高更明显,与5d时比较差异有统计学意义(均P<0.05)。②各组CA1区bFGF表达:PTZ组各时点均有明显表达,且随时间延长而表达不断增高,各时点比较差异有统计学意义(均P<0.01),与正常对照组比较差异有统计学意义(均P<0.01);TPM组在5d时与正常对照组比较差异有统计学意义(P<0.01),而10d、15d时逐渐下降,接近正常对照组水平。③各组CA3区bFGF表达:5d时3组比较差异无统计学意义。但PTZ组和TPM组在10d时与正常对照组比较差异有统计学意义(P<0.01),PTZ组在15d时和TPM组及正常对照组比较差异有统计学意义(均P<0.01)。(3)病理形态学改变:PTZ组和TPM组的海马CA1、CA3区尤其是CA1区可见较多神经元发生变性和坏死,PTZ组更显著。结论PTZ点燃过程中海马bF-GF表达增高,尤其在CA1区,且随时间延长有表达不断增高的趋势。TPM可能通过减少海马神经元损伤而明显下调海马CA1、CA3区bFGF的表达。

Objective To determine whether Topiramate （TPM） has an effect on basic fibroblast growth factor （bFGF） expression in hippocampus in a chronic kindling rat model of epilepsy. Methods Chronic kindling rat models were established by pentetrazole （PTZ） and divided into three groups： PTZ group, TPM group and normal control group. Each group then divided into three subgroups according to different time point of kindling （5, 10 and 15 d ）. The expressions of bFGF in CA1, CA3 and dentate gyrus areas of hippocampus were detected by immunohistochemistry method. The cellular morphologic changes were observed by HE staining method. Results （1） There was no difference of epileptic praxiology between PTZ and TPM groups. （2） Compared with normal control group, bFGF-positive cells in dentate gyrus in PTZ group and TPM group were increased significantly at each time point （ all P 〈 0. 01 ）, especially at 10 and 15 d, which were more than 5 d （ all P 〈 0. 05 ）. bFGF expressions in CA1 area in PTZ group had a total increasing trend by time, and they were more than normal control group （all P 〈 0. 01 ）. bFGF expressions in CA1 area in TPM group increased at 5 d, which was a significant difference compared with control group （P〈0.01）, then decreased to normal group level at 10 and 15 d. In CA3 area,there was no difference of bFGF expression among normal group, PTZ and TPM groups at 5 d. But this expression increased in PTZ and TPM groups at 10 d （ P 〈 0. 01 ） , and only PTZ group increased at 15 d （ P 〈 0. 01 ）. （ 3 ） Degeneration and necrosis of neurons in CA1 and CA3 areas （especially in CA1 area） were found beth in PTZ group and TPM group. This change was more obvious in PTZ group. Conehtsion bFGF expression is increased in hippocampus during kindling by pentetrazole especially in CA1 area and there is an increasing trend by time. Topiramate can downregulate bFGF expression in CA1 and CA3 areas of hippocampus by decreasing neuron lesions.