雌激素对戊四唑致痫大鼠海马内GABA和P38的影响

Effects of estrogen on GABA and P38 in the hippocampus of PTZ-induced epileptic rats

目的:分析月经性癫痫中,雌激素对大鼠海马内γ-氨基丁酸(γ-amiobutyricacid,GA BA)和P38的影响,探讨雌激素促癫痫发作的作用机理。方法:利用去卵巢(ovaiectomized,OVX)SD大鼠,用雌激素替代疗法及戊四唑(petylenetetrazole,PTZ)致痫,诱发大鼠癫痫发作,并采用免疫组织化学技术,对大鼠背侧海马不同脑区GABA和P38的免疫反应产物进行观察。结果:(1)GABA免疫组化检测结果显示,实验对照组(OVX+NS+PTZ)与空白对照组(OVX+NS+NS)相比及实验给药组(OVX+E2+PTZ)与实验对照组相比,背侧海马门区内GABA免疫反应阳性神经元数目均显著性减少。(2)P38免疫反应产物的观察:其免疫反应产物呈特征性点状或颗粒状。在CA1区始层和辐射层、CA3区透明层,空白对照组与实验对照组相比免疫反应强度无明显变化,实验给药组比实验对照组免疫反应增强。在齿状回分子层,3组的免疫反应强度无明显变化。结论:雌激素使海马门区GABA含量减少,从而降低了GABA对癫痫发作的抑制作用,增强了癫痫发作的敏感性。雌激素可使背侧海马CA1区始层和辐射层、CA3区透明层P38的表达增加(即使该区的突触密度增加),从而增加了海马内兴奋性递质的释放,使海马内的兴奋性增强。

Aim: To study effects of estrogen on GABA and P38 in the hippocampus of menstrual epilepsy rats ,and this will supply the basis for the mechanisms that estrogen enhances epileptic seizures. Methods: Estrogen-replace therapy was used ,and epileptic seizures were induced by PTZ in ovaiectomized SD female rats. GABA and P38 immunoreactive products were observed in different brain areas of dorsal hippocampus of rats. Results: 1) Results of GABA immunohistochemistry:GABA positive neurons significantly decreased in hila of dorsal hippocampus of OVX rats in PTZ treated groups as compared with control groups.There was also significantly decrease of GABA positive neurons in E2 treated groups as compared with PTZ treated groups. 2)Immunoreactive products of P38 observation: In stratum oriens and stratum radiatum of CA1 area and stratum lucidum of CA3, the immunoactive intensities had no significant changes in control group compared with PTZ treated group and stronger in E2 treated group compared with PTZ treated group. However, that of molecular layer of dentate gyrus had no significant changes among three groups. Conclusion:1) Behavior observation indicated that the estrogen enhanced significantly epileptic seizures. 2) The estrogen reduced the quantity of GABA in hilus area of dorsal hippocampus,thereby lowered the inhibiting ability of GABA on epileptic seizure, and enhanced epileptic seizures sensibility. 3)Estrogen increased the contents of P38 in stratum oriens and stratum radiatum of CA1 and stratum lucidum of CA3 (which meaned the increase of synaptic density). That increased the release of excitable neurotransmitters which enhanced the excitability in hippocampus. That might be one of the mechanisms of estrogen effects on the enhancement of epileptic susceptibility.