过表达Sirt1调节胶原蛋白诱导的关节炎细胞因子平衡  

The cytokine homeostasis was regulated by over-expression of Sirt1 in collageninduced arthritis mice

作　　者：丁永利[1] 陈星[1] 蔡一强[1] 赵明明[1] 姜勇[1] 

机构地区：[1]河南中医学院第一附属医院骨伤科,河南郑州450000

出　　处：《细胞与分子免疫学杂志》2014年第10期1034-1038,共5页Chinese Journal of Cellular and Molecular Immunology

摘　　要：目的研究过表达去乙酰化酶1(Sirtl)对2型胶原蛋白诱导的关节炎(CIA)小鼠细胞因子的影响。方法构建CIA模型,用携带Sirt1基因的重组腺病毒感染CIA小鼠,观察关节炎指数的变化。ELISA测定促炎因子白细胞介素1β(IL-1β)、肿瘤坏死因子-α(TNF-α)和IL-17以及抑炎因子IL-4和IL-10的含量。实时定量PCR(qRT-PCR)测定基质金属蛋白酶13(MMP-13)和基质金属蛋白酶抑制剂-1(TIMP-1)的表达。Western blot法检测p65和乙酰化p65蛋白的表达。结果与对照组相比,Ad-Sirt1感染组降低了小鼠关节炎指数,同时显著降低了IL-1β、TNF-α和IL-17的含量,增加了IL-4和IL-10的含量。Ad-Sirt1感染组下调了MMP-13的mRNA表达,上调了TIMP-1的mRNA表达。Ad-Sirt1感染组使p65蛋白乙酰化水平下降。结论过表达的Sirt1有调节CIA小鼠关节炎细胞因子平衡的作用。Objective To investigate the effects of over-expression of Sirt1 on cytokines in the collagen type 2-induced arthritis（ CIA） mice. Methods The female DBA /1 mouse CIA model was establised by subcutaneous injection of collagen type 2. Recombinant adenovirus carrying Sirt1 gene was infected into CIA mice through tail vein injection. The effects of over-expression of Sirt1 on CIA mice were assessed by measuring arthritis index. The serum levels of cytokines including interleukin 1β（ IL-1β）,tumor necrosis factor α（ TNF-α）,IL-17,IL-4 and IL-10 in CIA mice were examined by ELISA. The mRNA levels of Sirt1,matrix metalloproteinase-13（ MMP-13） and tissue inhibitor of metalloproteinase-1（ TIMP-1） were detected by real-time quantitative PCR（ qRT-PCR）. The protein levels of NF-κB subunit p65 and acetylated p65 were determined by Western blotting. Results Compared with control groups,over-expression of Sirt1 significantly ameliorated the symptoms of arthritis in CIA mouse. Furthermore, proinflammatory factors（ IL-1β, TNF-α, IL-17） decreased while anti-inflammatory factors（ IL-4 and IL-10） increased in CIA mice. The over-expression of Sirt1 significantly down-regulated MMP-13 mRNA level and up-regulated TIMP-1 mRNA level. Additionally,the over-expressed Sirt1 reduced acetylation of p65. Conclusion Over-expression of Sirt1 may regulate the balance of cytokines in CIA mice.

关 键 词：SIRT1 类风湿性关节炎 核因子ΚB 细胞因子 

分 类 号：R593.2[医药卫生—内科学] Q786[医药卫生—临床医学]