川芎嗪通过AMPK-NFκB信号通路抑制BV-2小胶质细胞促炎性细胞因子基因表达  

Tetramethylpyrazine Inhibits Gene Expression of Proinflammatory Cytokines from BV-2 Microglial Cells by Adenosine Monophosphate-Activated Protein Kinase/Nuclear Factor Kappa B Pathway

作　　者：刘长安[1] 朱洁[1,2] 蔡标[1] 汪天明[1] 黄金玲[1,2] 

机构地区：[1]安徽中医药大学中西医结合临床学院,安徽合肥230038 [2]安徽省中医药科学院中西医结合研究所,安徽合肥230038

出　　处：《安徽中医药大学学报》2014年第3期76-80,共5页Journal of Anhui University of Chinese Medicine

基　　金：安徽省高等学校省级优秀青年人才基金项目(2012SQRL103);安徽中医药大学自然科学研究基金项目(2013zr007);安徽省高校省级自然科学研究项目(KJ2013Z160)

摘　　要：目的观察川芎嗪(tetramethylpyrazine,TMP)对Aβ25-35诱导的BV-2小鼠小胶质细胞促炎性细胞因子基因表达及对一磷酸腺苷激活的蛋白激酶(adenosine monophosphate-activated protein kinase,AMPK)-核因子κB(nuclear factor kappa B,NFκB)信号通路的影响。方法采用Aβ25-35激活BV-2细胞的炎性反应,测定TMP高、中、低剂量(终浓度分别为100、30、10μmol/L)对Aβ25-35诱导的BV-2细胞白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factorα,TNF-α)及诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)mRNA表达水平的影响。在AMPK激活剂(AICAR)及抑制剂(化合物C)存在下,检测TMP对AMPK及p65(NFκB亚基)磷酸化的影响。结果 TMP高、中剂量可明显抑制BV-2细胞中IL-1β、IL-6、TNF-α和iNOS基因mRNA表达水平(P<0.01),高剂量TMP可激活BV-2细胞中AMPK(P<0.01),并抑制p65磷酸化(P<0.01)。结论 TMP通过激活BV-2细胞中AMPK活性,抑制NFκB活化,进而抑制促炎性细胞因子基因的表达。Objective To observe the effects of tetramethylpyrazine （TMP） on the gene expression of proinflammatory cytokines induced by Aβ25- 35 and the adenosine monophosphate-activated protein kinase （AMPK）/nuclear factor kappa B （NF-κB） pathway in mouse BV-2 microglial cells. Methods BV-2 cells were treated with Aβ25- 35 to induce inflammatory response. The mRNA expression of interleukin-1β （IL- 1β）, interleukin-6 （IL-6）, tumor necrosis factor-α （TNF-α）, and inducible nitric oxide synthase （iNOS） in BV-2 cells were measured in the presence of high-, middle-, or low-dose TMP （100, 30, or 10 μmol/L）. The effects of TMP on the phosphorylation of AMPK and p65 （a subunit of NF-κB） were evaluated in the presence of AMPK activator （AICAR） and inhibitor （Compound C）. Results High- and middle-dose TMP significantly inhibited the mRNA expression of IL-1β, IL-6, TNF-α, and iNOS in BV-2 cells （P〈 0.01）. High-dose TMP activated AMPK in BV-2 cells （P〈0.01）, but inhibited the phosphorylation of p65 （P〈0.01）. Conclusion TMP can inhibit the mRNA expression of proinflammatory cytokines by activating AMPK and inhibiting the activation of NF-κB in BV-2 cells.

关 键 词：川芎嗪 BV-2细胞 淀粉样蛋白β 促炎性细胞因子 基因表达 AMPK 核因子κB 

分 类 号：R459.5[医药卫生—治疗学]