雌激素膜受体激动剂G1对脂多糖诱导小胶质细胞iNOS表达影响  

THE EFFECT OF MEMBRANOUS ESTROGEN RECEPTOR AGONIST G1 ON LIPOPOLYSACCHARIDE-INDUED iNOS EXPRESSION IN BV2 MICROGLIA

作　　者：高先琦 孙宪昌[1,2] 姜明春[1,2] 陈筱涵 王雅迪[1] 陈文芳[1] 

机构地区：[1]青岛大学医学院生理学教研室,山东青岛266071 [2]泰山医学院生理学教研室

出　　处：《青岛大学医学院学报》2015年第4期390-391,394,共3页Acta Academiae Medicinae Qingdao Universitatis

基　　金：国家自然科学基金资助项目(31271150;30971004)

摘　　要：目的探讨G蛋白耦联雌激素受体（GPER）激动剂G1对脂多糖（LPS）诱导的BV2小胶质细胞诱导型一氧化氮合酶（iNOS）表达的影响。方法 BV2小胶质细胞常规培养,LPS诱导炎症反应,用GPER激动剂G1或阻断剂G15与LPS共培养。MTT法检测BV2细胞活力,实时反转录聚合酶链反应（real time RT-PCR）检测iNOS基因的表达。结果 LPS（0.1和1.0μg）对BV2细胞活力没有明显的影响（P〉0.05）。0.1及1.0μg的LPS均可明显增加iNOS的基因表达,1.0μg LPS组作用最为明显（F=19.10,q=4.018~8.732,P〈0.05）。与LPS组相比,G1预给药组能够明显抑制LPS对iNOS基因的诱导作用（F=35.79,q=7.724,P〈0.01）。与G1预给药组相比,此作用可以被GPER阻断剂G15所阻断（F=35.79,q=5.434,P〈0.05）。结论 GPER的激动剂G1具有抑制LPS对BV2小胶质细胞的激活作用,此为中枢神经系统炎症相关疾病的治疗提供了新的靶点。Objective To investigate the effect of membranous estrogen receptor（G protein-coupled estrogen receptor,GPER）agonist G1 on lipopolysaccharide（LPS）-induced inducible nitric oxide synthase（iNOS）expression in BV2 microglia.Methods BV2 microglial cells were cultured and induced inflammatory response by LPS in the presence or absence of GPER agonist G1 or GPER antagonist G15.The cell viability was observed via MTT assay.Real time PCR was used to detect the gene expression of iNOS. Results LPS（0.1and 1.0μg）did not affect the viability of the BV2 microglial cells（P0.05）.Both 0.1and 1.0μg LPS treatment resulted in the increase of the gene expression of iNOS,and the most effective dosage being 1.0μg LPS（F=19.10,q=4.018-8.732,P0.05）.Compared with the LPS group,pretreatment with G1 could significantly inhibit the iNOS mRNA level induced by LPS（F=35.79,q=7.724,P0.01）,and this effect could be blocked by G15 compared with the G1group（F=35.79,q=5.434,P0.05）. Conclusion G protein-coupled estrogen receptor agonist G1 can inhibit the LPS-induced activation of BV2 microglia.These data provide a novel therapeutic target for the treatment of inflammatory-related diseases in the central nervous system.

关 键 词：G蛋白耦联雌激素受体 脂多糖 诱导型一氧化氮合成酶 BV2小胶质细胞 聚合酶链反应 

分 类 号：R96[医药卫生—药理学]