不同剂量氯喹对戊四氮慢性致痫大鼠脑内谷氨酸受体2表达的影响

Effect of different dose of Chloroquine on GluR2 expression in the brain of rats with epilepsy induced by pentylenetetrazole

目的观察不同剂量氯喹对戊四氮(PTZ)慢性致痫大鼠脑内α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体(AMPA-GluR2)表达的影响,探讨氯喹在癫痫发生发展过程中的作用。方法健康雄性SD大鼠50只,随机分为对照组(10只,腹腔注射生理盐水,40 mg/kg)、PTZ致痫组(10只,腹腔注射0.5%PTZ溶液,40 mg/kg)、氯喹不同剂量治疗组(1、2、3组,各10只,分别腹腔注射0.5%氯喹溶液20、40、60 mg/kg)。观察大鼠行为学表现,应用Western blot和免疫组织化学法检测氯喹对各组GluR2表达的影响。结果 PTZ致痫组GluR2表达明显减少,与对照组比较,差异有统计学意义(P<0.05);氯喹可增强GluR2的表达,PTZ致痫组与氯喹治疗2、3组比较,差异有统计学意义(P<0.05)。结论氯喹能够剂量依赖性地调节GluR2表达,提示氯喹可通过其对GluR2的调节作用达到抗癫痫效应。

Objective To observe the effect of different dose of Chloroquine on AMPA-GluR2 expression in the brain of rats with epilepsy induced by pentylenetetrazole, and to explore the role of Chloroquine in epileptogenesis. Methods 50 male adult Sprague-Dawley （SD） rats were randomly divided into control group （n=10, intraperitoneal injection of saline solution, 40 mg/kg）, pentylenetetrazole （PTZ） group （n=10, intraperitoneal injection of 0.5% pentylenetetrazole, 40 mg/kg）, Chloroquine intervening groups （group one, two, three, n=10, intraperitoneal injection of 0.5% Chloroquine 20, 40, 60 mg/kg respectively）. The behavior of rats was observed. Expression of GluR2 in the brain of rats was examined by Western Blot and immunohistochemistry methods. Results GluR2 level in PTZ group was lower as compared with control group （P 〈 0.05）. Chloroquine could increased the expression of GluR2, there were significant differences between Chloroquine intervening two, three groups and PTZ group （P 〈 0.05）. Conclusion Chloroquine can moderate the expression of GluR2 by dose dependent, which suggests that Chloroquine may be through its adjuste effect on GluR2 to achieve the antiepileptic effect.