大黄酚对氨诱导星形胶质细胞肿胀及谷氨酸再摄取抑制的影响及其机制研究  

Effects of chrysophanol on ammonia-induced cell swelling and glutamate uptake inhibition in cultured astrocytes and the study of its mechanisms

作　　者：薛占霞[1] 高永山[2] 沈丽霞[1] 武雪亮[3] 

机构地区：[1]河北北方学院药学系药理教研室,河北张家口075000 [2]河北北方学院附属第一医院心脏外科,河北张家口075000 [3]河北北方学院附属第一医院血管腺体外科,河北张家口075000

出　　处：《中国临床药理学杂志》2016年第1期59-61,64,共4页The Chinese Journal of Clinical Pharmacology

基　　金：河北省教育厅优秀青年基金资助项目(Y2012002);河北省自然科学基金资助项目(H2012405016);河北北方学院创新人才基金资助项目(CXRC1325)

摘　　要：目的探讨大黄酚对氨诱导星形胶质细胞肿胀及谷氨酸再摄取抑制的影响及其机制研究。方法原代培养小鼠星形胶质细胞,随机分为正常组、模型组、3个剂量大黄酚实验组(0.1,1.0,10.0μg·m L^(-1))和6个对照组[包括一氧化氮合酶抑制剂——L-NAME 250μmol·L^(-1),维生素E 100μmol·L^(-1),超氧化物歧化酶(SOD,25 U·m L^(-1)),细胞外信号调节激酶1/2(ERK1/2)抑制剂——UO126 10μmol·L^(-1),P38MAPK抑制剂——SB239063 10μmol·L^(-1),JNK1/2/3抑制剂——SP600125 1μmol·L^(-1)]。药物处理细胞48 h,通过测定细胞内水的体积来检测细胞体积,处理72 h后通过同位素标记法检测谷氨酸再摄取,RT-PCR法检测谷氨酸/天门冬氨酸转运体(GLAST)mRNA表达。结果大、中2个剂量大黄酚可改善氨诱导星形胶质细胞肿胀及谷氨酸摄取抑制,作用程度与对照组类似。同时大、中2个剂量大黄酚可逆转氨诱导GLAST mRNA表达下调作用。结论大黄酚可能通过抗氧化应激及抑制有丝裂原活化蛋白激酶(MAPKs)磷酸化来改善氨诱导星形胶质细胞功能障碍。Objective To study the effects of chrysophanol（ Chry） on ammonia-induced cell swelling and gultamate uptake inhibition in cultured astrocytes and its signaling pathways. Methods Primary cultured mouse astrocytes were divided into normal group,model group,three Chry test group（ 0. 1,1. 0,10. 0 μg · m L^（-1）） and six positive control group[L-NAME 250 μmol·L^（-1）,vitamin E 100 μmol·L^（-1）,superoxide dismutase（ SOD） 25 U · m L^（-1）,extracellular regulated kinase1 /2（ ERK1 /2） inhibitor UO126 10 μmol · L^（-1）,P38 MAPK inhibitor SB239063 10 μmol · L^（-1）, JNK1 /2 /3 inhibitor SP6001251 μmol·L^（-1）]. Cultured astrocytes treated for 48 h,cell volume were measured by measuring the volume of water in cell and gultamate uptake were measured by the isotope labeling method after 72 h. The glutamate /aspartate transporter（ GLAST） mRNA expression was detected by RT-PCR. Results Ammonia-induced astrocytes swelling and gultamate uptake inhibition and GLAST mRNA expression downregulation were reduced by moderate and lager doses Chry,which similar to the positive control. Conclusion Chry may improve the ammonia-induced astrocytes dysfunction by againsting oxidative stress and inhibiting the MAPKs phosphorylation.

关 键 词：大黄酚 星形胶质细胞肿胀 氧化应激/硝化应激 谷氨酸摄取抑制 

分 类 号：R285.5[医药卫生—中药学] R977.9[医药卫生—中医学]