Inhibition of experimental arthritis in mice by small interfering RNA targeting histone deacetylase 1 (siHDAC1) using in vivo electroporation method

我们使用体内电穿孔方法检测了靶向组蛋白去乙酰化酶1（siHDAC 1）的siRNA的治疗效果。关节内注射siHDAC不影响小鼠中抗胶原抗体诱导的关节炎的发红或爪肿胀。然而，在用siHDAC 1处理的膝关节中，滑膜增殖、骨侵蚀和关节软骨退化比对照组和非特异性siRNA组中更轻。TUNEL染色显示siHADC组滑膜组织中阳性细胞数量增加。siHDAC处理组滑膜成纤维细胞HDAC 1表达明显降低，而IL-6、TNF和MMP-3 mRNA表达与对照组和非特异性siRNA组相比无显著性差异。我们的研究结果表明，关节内siHDAC 1与电穿孔的治疗效果是通过诱导滑膜细胞凋亡的抗增殖特性。

We examined the therapeutic effects of siRNA targeting histone deacetylase 1 (siHDAC1) using in vivo electroporation method. Intraarticular injection of siHDAC did not affected redness or paw swelling of anti-collagen antibody-induced arthritiis in mice. However, synovial proliferation, bone erosion, and degeneration of articular cartilage were milder in the knee joints treated with siHDAC1 than in the control group and the non-specific siRNA group. TUNEL stain revealed increased number of positive cells in the synovial tissue of siHADC group. Decreased HDAC1 expression was noted in the synovial fibroblasts isolated from arthritic knee joints treated by siHDAC, but no significant difference was shown by RT-PCR in IL-6, TNF, and MMP-3 mRNA expression with those from control and non-specific siRNA group. Our results suggested therapeutic effects of intraarticular siHDAC1 with electroporation was derived by its anti-proliferative property by induction of synovial cell apoptosis.