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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 effect of overexpression of sirtl on cytokines in type 2 collagen induced arthritis (CIA) mice. Methods CIA model was constructed. CIA mice were infected with recombinant adenovirus carrying Sirt1 gene and the changes of arthritis index were observed. The levels of IL-1β, TNF-α and IL-17 and the anti-inflammatory cytokines IL-4 and IL-10 were determined by ELISA. Real-time quantitative PCR (qRT-PCR) was used to detect the expression of matrix metalloproteinase-13 (MMP-13) and matrix metalloproteinase-1 (TIMP-1) Western blot was used to detect the expression of p65 and acetylated p65 protein. Results Compared with the control group, the Ad-Sirt1 infection group decreased the arthritis index, significantly reduced the levels of IL-1β, TNF-α and IL-17 and increased the contents of IL-4 and IL-10. Ad-Sirt1 infection down-regulated MMP-13 mRNA expression and up-regulated TIMP-1 mRNA expression. Ad-Sirt1 infection decreased p65 protein acetylation. Conclusion Overexpression of Sirt1 can regulate the balance of arthritis cytokines in CIA mice.