α-亚麻酸的体外抗炎作用机制研究  

Studies on in vitro anti-inflammatory mechanism of α-linolenic acid

作　　者：任杰[1] 杨泽华[1] 郑圣顕 胡昆[1] 

机构地区：[1]江苏工业学院化学化工学院,江苏常州213164 [2]庆熙大学药学院药理学和临床药理学系

出　　处：《云南大学学报（自然科学版）》2009年第S1期419-426,共8页Journal of Yunnan University(Natural Sciences Edition)

基　　金：江苏工业学院博士启动基金资助

摘　　要：α-亚麻酸(ALA)显示了潜在的抗炎活性,为了探求其体外抗炎机制,检测ALA对脂多糖(LPS)刺激的RAW264.7巨噬细胞产生的一氧化氮(NO)和前列腺素E2(PGE2)的作用,发现ALA对NO和PGE2的产生有很强的抑制作用.通过逆转录聚合酶链反应(RT-PCR)和Western blot方法,发现ALA也显著抑制了诱导型一氧化氮合成酶(iNOS)、环氧合酶2(COX-2)和肿瘤坏死因子(TNF-α)的mRNA水平和蛋白的表达.为了进一步探索ALA抑制iNOS基因表达的机制,通过电泳迁移率变动分析法(EMSA)检测了ALA对LPS诱导的核因子-κB(NF-κB)激活的作用.LPS诱导的NF-κBDNA结合活性被ALA显著地抑制.这个作用是通过抑制抑制因子-κBα(I-κBα)的磷酸化和降解以及抑制丝裂原激活蛋白激酶的磷酸化调节的.总之,这些结果表明ALA通过封锁NF-κB和MAPKs的激活抑制了巨噬细胞中LPS诱导的NO和PGE2的产生,并且抑制了iNOS,COX-2和TNF-α的基因表达.α-Linolenic acid exhibits potent anti-inflammatory activity with unknown mechanism.To elucidate the molecular mechanisms of ALA on pharmacological and biochemical actions in inflammation,we examined the effect of ALA on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in the murine macrophages cell line,RAW 264.7.We found that ALA has a strong inhibitory effect on the production of NO.ALA also inhibited inducible nitric oxide synthase (iNOS),cyclooxygenase-2 (COX-2) and tumor necrosis factor-alpha (TNF-α) gene expressions induced by LPS.In order to explore the mechanisms associated with the inhibition of iNOS gene expression by ALA,we investigated its effect on LPS-induced nuclear factor-κB (NF-κB) activation.Treatment with ALA reduced a translocation of NF-κB subunit and NF-κB-dependent transcriptional activity.The activation of NF-κB was inhibited by prevention of the degradation of inhibitory factor-κBα (I-κBα).We also found that ALA inhibited LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs).Taken together,these results suggest that ALA downregulates inflammatory iNOS,COX-2 and TNF-α gene expressions through the blocking of NF-κB and MAPKs activations in LPS-stimulated RAW 264.7 cells,which may be the mechanistic basis for the anti-inflammatory effect of ALA.

关 键 词：Α-亚麻酸 抗炎 一氧化氮 诱导型一氧化氮合成酶 肿瘤坏死因子-Α 核因子-ΚB 丝裂原激活蛋白激酶 

分 类 号：Q946[生物学—植物学]