毛果芸香碱致慢性癫大鼠脑内药物转运体表达的变化

目的研究有机阴离子转运多肽亚型2(Oatp2)及P-糖蛋白(P-gp)在氯化锂-毛果芸香碱诱导的慢性癫大鼠脑组织中的表达。方法采用氯化锂-毛果芸香碱诱发Wistar大鼠慢性癫模型,免疫组织化学法检测其脑内Oatp2、P-gp的分布及表达情况。结果Oatp2及P-gp免疫反应阳性物质主要定位于脉络丛上皮细胞膜及脑血管内皮细胞膜,神经细胞膜也可见染色;性大鼠脑内Oatp2的表达低于正常大鼠(P<0.05);而P-gp的表达高于正常大鼠(P<0.05)。结论慢性癫大鼠脑内同时存在药物转运体Oatp2及P-gp的表达,两者表达变化相反。在癫病理过程中,Oatp2可能具有与P-gp不同的作用。

Changes of Drug Transporters Expression in Brains of Chronic Epileptic Rats Induced by Lithium-Pilocarpine

Objective To explore the expression of drug transporter organic anion transporting polypeptide2(Oatp2) and P-glycoprotein(P-gp) in brains of chronic epileptic rats induced by lithium-pilocarpine.Methods Chronic epilepsy modles were elicited after status epilepticus(SE) induced by lithium-pilocarpine in adult Wistar rats.The expressions of Oatp2 and P-gp were detected by immuno-histochemistry(SABC) method.Results Positive expression of Oatp2 was predominantly in the plexus epithelial cells and(blood-brain) barrier endothelial cells.Weak staining for Oatp2 was also detected in the neurocyte.In contrast,apparent expression of(P-gp) was seen in brain capillary and neurocyte only.Compared with normal control rats,expression of Oatp2 on the plexus epithelial cells and brain capillary in chronic epileptic rats was significantly decreased(P<0.05).In contrast,expression of P-gp was obviously higher in chronic epileptic rats than that in control rats(P<0.05).Conclusions There is a different pattern of expression of Oatp2 and P-gp in brains of chronic epileptic rats induced by lithium-pilocarpine,Oatp2 maybe play a different role as P-gp in intractable epilepsy.