百草枯诱导的慢性帕金森病模型大鼠血脑屏障和P-gP变化的研究

目的：探讨百草枯诱导的慢性帕金森病模型中大鼠血脑屏障功能和P-糖蛋白表达的变化。方法：随机将动物分成3组：对照组（生理盐水注射组）和模型组（百草枯注射4周、8周组）。以免疫组织化学染色方法显示各组中脑酪氨酸羟化酶（TH）阳性细胞、免疫印迹检测TH蛋白表达和P-糖蛋白表达、Belyaevs＇法使用EB测定BBB通透性。进行统计学分析。结果：与对照组相比，模型组TH阳性神经元和TH蛋白表达较对照组明显减少（P〈o．05）；模型组大鼠BBB的通透性显著增加（P〈0．05）；与对照组比较，模型组P-gP表达显著降低（P〈0．05）。结论：百草枯可通过使TH阳性神经元和TH蛋白表达减少，诱导大鼠慢性帕金森病模型；同时导致BBB通透性增加和P-糖蛋白表达下降，百草枯可能通过影响BBB通透性和P-糖蛋白的表达诱导帕金森病。

Study on the alteration of blood-brain barrier function and expression of P-gp in rats with paraquat-induced chronic parkinson disease

Objective：To investigate the alteration of blood-brain barrier （BBB） measured by EB and expression of P-gp in paraquat-induced chronic Parkinson disease. Method： Thirty male Wistar rats were randomly divided into three groups： normal group（physiologic saline group） and two model groups （paraquat 4 weeks and 8 weeks group） ,The number of tyrosine hydroxylase （TH）- positive neurons were observed by immunohistochemistry, TH protein and the P-gp expressions were examined by immuno blotting, the BBB permeability was assessed by Belyaevs＇ method. Result： Compared with normal group, TH-positive neurons and the expressions of TH in the model groups were obviously reduced （P〈0.05） ;the BBB permeability of the model groups was obviously deduced compared with normal group （P〈0. 05）, P-gp protein expression in the model groups was downregulated obvious- ly（P〈0.05）. Conclusion：The chronic PD modal were induced by paraquat which leaded to the down-regulation of TH-positive neurons and the expressions of TH. At the same time, paraquat induced the increasion of BBB permea- bility and reduced P-gp protein expression. Paraquat might have certain effect on chronic PD by regulating BBB permeability and P-gp protein expression.