CART肽通过激活ERK抑制氧糖剥夺诱导的星形胶质细胞AQP-4上调  

CART peptide inhibits AQP-4 expression in astrocytes of mice with oxygen-glucose deprivation injury by ERK signaling pathway

作　　者：刘丽冰 王伟[1] 李烁 祝世功[2] LIU Li-bing;WANG Wei;LI Shuo;ZHU Shi-gong(Weifang Yidu Central Hospital,Qingzhou 262500,China;School of Basic Medical Science,Peking University,Beijing 100191,China)

机构地区：[1]潍坊市益都中心医院,山东青州262500 [2]北京大学医学部基础医学院,北京100191

出　　处：《中国病理生理杂志》2019年第10期1864-1868,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81471254; No.81171081)

摘　　要：目的:探讨可卡因-苯丙胺调节转录(CART)肽抑制星形胶质细胞氧糖剥夺(OGD)性损伤及调节水通道蛋白4(AQP-4)表达的分子机制。方法:体外培养新生ICR小鼠大脑皮层星形胶质细胞,通过胶质纤维酸性蛋白(GFAP)免疫荧光染色鉴定细胞。所得细胞随机分为4组:对照组、模型组、CART组和CART+PD98059(ERK信号通路特异性阻断剂)组,MTT法检测星形胶质细胞活力,Western blot检测ERK及AQP-4的表达。结果:OGD处理后,CART肽能显著提高OGD后星形胶质细胞的活力(P<0.01);CART肽能够提升星形胶质细胞内ERK的磷酸化水平(P<0.05);PD98059能够阻断CART肽诱导的ERK磷酸化(P<0.01),并减弱CART肽抑制AQP-4表达的作用(P<0.05)。结论:CART肽提高OGD处理后星形胶质细胞的活力,并通过激活ERK通路抑制OGD处理后细胞AQP-4的表达。AIM:To study the protective effect of cocaine-and amphetamine-regulated transcript(CART)peptide on astrocytes of mice with oxygen-glucose deprivation(OGD)injury and the related mechanism involving regulation of aquaporin 4(AQP-4)expression.METHODS:Mouse cortical astrocytes from neonatal ICR mice were cultured,and were identified with immunofluorescence staining of glial fibrilillary acidic protein(GFAP).The astrocytes were divided into 4 groups:control group,model group,CART group and CART+PD98059 group.The viability of the cells were measured by MTT assay.The protein levels of ERK and AQP-4 were analyzed by Western blot.RESULTS:CART peptide induced a significant increase in the cell viability after OGD(P<0.01).CART peptide enhanced the phosphorylation level of ERK after OGD,which was inhibited by PD98059 pretreatment(P<0.05).PD98059 also inhibited down-regulation of AQP-4 expression induced by CART peptide after OGD(P<0.05).CONCLUSION:CART peptide enhances the viability,and inhibits AQP-4 expression in the astrocytes of mice after OGD through activating ERK signaling pathway.

关 键 词：可卡因-苯丙胺调节转录肽 水通道蛋白4 星形胶质细胞 氧糖剥夺 ERK信号通路 

分 类 号：R363.2[医药卫生—病理学] R329.25[医药卫生—基础医学]