不同剂量氯喹对慢性致痫大鼠脑内星形胶质细胞增殖及GFAP表达的影响  

Effects of different doses of chloroquine on astrocyte proliferation and expression of GFAP in rat brain with chronic epilepsy

作　　者：李宁宁[1] 吴淑华[1] 刘鲁英[1] 杨东霞[1] 于宁[1] 

机构地区：[1]滨州医学院病理学教研室,滨州市256603

出　　处：《滨州医学院学报》2010年第2期85-89,共5页Journal of Binzhou Medical University

基　　金：山东省教育厅科技计划资助项目(J08LG14)

摘　　要：目的探讨不同干预剂量氯喹对慢性致痫大鼠脑内星形胶质细胞增殖、细胞形态、星形胶质细胞酸性蛋白(GFAP)表达情况的影响。方法戊四氮(PTZ)点燃致大鼠慢性癫痫模型,随机分为对照组、癫痫组、氯喹干预组(按不同剂量分4组),共6组。采用流式细胞术检测各组大鼠脑皮质和海马区星形胶质细胞(Ast)增殖周期变化;应用免疫组化检测Ast增殖、形态及GFAP表达水平。结果PTZ致痫组皮质和海马区不仅星形胶质细胞形态有改变,而且与对照组相比增殖活性明显增强(P<0.01)。氯喹干预各组细胞增殖周期、GFAP免疫反应阳性数目和积分光密度值与癫痫组相比差异均有显著性(P<0.05、P<0.01);随氯喹干预剂量增高,各项检测指标趋于正常,高剂量组与癫痫组比较差异有极显著性(P<0.01),而与正常对照组相比差异无统计学意义(P>0.05)。结论不同剂量氯喹对慢性癫痫的干预作用呈先增加后减弱的趋势,在达到一定作用剂量后,其作用不随剂量增加而增加,提示选择合理的剂量可提高疗效,减少副作用,对于癫痫治疗有重要意义。Objective To explore the effects of different doses of chloroquine on the astrocytes cell cycle,morphology and GFAP-positive integral optical density in the brain of rat with seizures.Methods Rats induced by pentylenetrazole with chronic seizures were randomly divided into control group,epilepsy group and chloroquine intervention group（divided into 4 groups according to different doses）,a total of 6 groups.each group detected the changes of astrocyte cycle by flow cytometry in cerebral cortex and hippocampus;The proliferation and morphology of Ast and the expression of GFAP were detected by immunohistochemistry.Results ①Compared with the control group,not only the morphology changed but also the proliferation activity significantly increased（P〈0.01） of astrocyte in PTZ-induced epileptic group.②There were significant differences of cell proliferation cycle,GFAP immunoreactive number between chloroquine intervention groups and the epilepsy group（P〈0.05,P〈0.01）.③ With the dose of chloroquine increased,no significant differences were observed compared with control group（P〈0.05）,but the difference between high-dose group and epilepsy group were significant（P〈0.01）.Conclusion Following the doses increase of chloroquine the effective enhanced,when the doses of chloroquine higher than a level,the effective keep stable,but,side effects of chloroquine improved.So chose reasonable dose for clinical treatment is significant.

关 键 词：氯喹 慢性癫痫 星形胶质细胞 细胞增殖 星形胶质细胞酸性蛋白 

分 类 号：R363.1[医药卫生—病理学]