慢性癫痫SD大鼠模型海马P-糖蛋白表达的研究

The Study of Expression of P-glycoprotein in Hippocampus in a Chronic Epileptic SD Rat Model

目的建立戊四氮点燃的慢性癫痫SD大鼠模型,观察海马P-糖蛋白(P-glycoprotein,P-gp)的表达,探讨难治性癫痫的可能耐药原因。方法以戊四氮(pentylenetetrazol,PTZ)亚抽搐剂量连续每天对SD大鼠进行腹腔注射,最长注射28 d,观察点燃率。应用免疫组化技术观察正常对照组、点燃组和未点燃组海马P-gp的表达。结果SD大鼠总点燃率达63.3%。正常对照组海马组织未见P-gp阳性细胞表达,未点燃组毛细血管管腔见少量P-gp的阳性细胞表达,而点燃组可见较多P-gp的阳性细胞表达,这些阳性标记主要位于毛细血管的管腔,少量胶质细胞也有表达,神经元未见表达,且点燃组阳性细胞表达较未点燃组明显增多,差异具有统计学意义(P<0.01)。结论慢性癫痫发作可以诱导P-gp的表达,发作强度越强,P-pg表达越高,特别是在毛细血管内皮细胞上的高表达,可能与癫痫耐药有关。

Objective To explore the relationship between the P-glycoprotein（P-gp） expression in hippocampus in the kindled model and the drug resistance in the intractable epilepsy. Methods The kindled model were prepared in Sprague-Dawley（SD） rats by constant intraperitoneal injection of pentylenetetrazol（PTZ） at subthreshold dosages. P-gp expression was detected in hippocampus from different groups of experimental rats by immunohistochemistry method. Results 63.3% rats were fully kindled. There was no P-gp positive signal in hippocampus in normal rats. Positive cells were detected in the nonkindled rats and in the kindled rats, especially in capillary endothelial Cells and some astrocytes, but not in neurons. P-gp expression in hippocampus was more increased in the kindled rats than that in the nonkindled rats （P〈0.01）. Conclusion Chronic seizures-induced overexpression of P-gp, especially in capillary endothelial cells could explain the drug resistance in intractable epilepsy.