阿魏酸对小胶质细胞炎性反应的抑制作用  

Inhibitory effect of ferulic acid on neuroinflammation in LPS-activated microglia

作　　者：吴建良[1] 沈敏敏[1] 杨水新[1] 王翔[2] 马增春[3] 

机构地区：[1]湖州市中心医院,浙江湖州313000 [2]湖州市第一人民医院,浙江湖州313000 [3]军事医学科学院放射与辐射医学研究所,北京100850

出　　处：《中国药理学通报》2015年第1期97-102,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金青年基金项目(No 81202936);湖州市科技计划项目(No 2013GY14)

摘　　要：目的：考察阿魏酸对脂多糖诱导的小鼠小胶质细胞炎性反应的抑制作用及其机制。方法采用脂多糖（ LPS）刺激小胶质细胞（ BV-2）活化,研究阿魏酸对炎症反应的抑制作用。采用硝酸还原酶法检测阿魏酸对一氧化氮（ nitric ox-ide, NO）的影响,定量PCR和蛋白印迹分析阿魏酸对诱导型一氧化氮合酶（ inducible nitric oxide synthase, iNOS）和环氧合酶-2（COX-2）的影响,定量PCR技术和ELISA分析阿魏酸对炎性因子白细胞介素-1β（ interleukin-1β, IL-1β）、白细胞介素-6（interleukin-6, IL-6）、肿瘤坏死因子-α（tumor necro-sis factor-α, TNF-α）的影响,进而检测阿魏酸对促分裂原活化蛋白激酶（ mitogen-activated protein kinases, MAPK）信号通路的影响。结果1．25～20μmol · L^-1的阿魏酸对细胞活性无明显影响。阿魏酸浓度依赖性降低NO的浓度,可以明显抑制iNOS、COX-2的基因和蛋白表达,明显抑制IL-1β、IL-6、TNF-α的表达,提前给予阿魏酸共同孵育对 LPS引起的ERK信号通路的磷酸化有抑制作用。结论阿魏酸具有抑制小胶质细胞活化,抑制神经性炎症的作用,其机制可能是阿魏酸通过ERK信号通路发挥对炎性分子的抑制作用。Aim To evaluate the effects of ferulic acid （ FA ） on lipopolysaccharide （ LPS ）-induced neuroin-flammation in microglia cells and its potential mecha-nisms. Methods Microglial activation was induced by stimulation with LPS, and the effects of FA pretreat-ment on microglial activation and production of proin-flammatory mediators, nitric oxide/iNOS were investi-gated. The role of the mitogen-activated protein kinases in the antiinflammatory actions of FA in LPS-stimulated microglia was further elucidated. Results Cell viabil-ity experiments revealed that FA did not produce cyto-toxicity in microglia. FA significantly inhibited LPS-in-duced production of tumour necrosis factor-alpha （ TNF-α） , interleukin-6 （ IL-6 ） , interleukin-1 beta （ IL-1β） , and nitric oxide （ NO ） . Protein and mRNA levels of COX-2 and inducible nitric oxide synthase （ iNOS） were also attenuated by FA. Further experi-ments on intracellular signalling mechanisms showed that inhibition of extracellular regulated kinase （ ERK） contributed to the anti-neuroinflammatory actions of FA. Conclusion The results suggest that FA inhibits LPS-induced microglial inflammation by partial targe-ting of ERK signalling and attenuation of ERK.

关 键 词：阿魏酸 小胶质细胞 神经性炎症 一氧化氮合酶 环氧合酶-2 炎性因子 

分 类 号：R-332[医药卫生] R322.81