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

我们用体内电穿孔法检测了siRNA靶向组蛋白去乙酰化酶1 （siHDAC1）的治疗效果。关节内注射siHDAC对小鼠抗胶原抗体性关节炎的红肿无明显影响。然而，与对照组和非特异性siHDAC1组相比，siHDAC1治疗的膝关节滑膜增生、骨侵蚀和关节软骨退行性变较轻。TUNEL染色显示siHADC组滑膜组织阳性细胞增多。经siHDAC处理的关节炎膝关节滑膜成纤维细胞中HDAC1表达降低，但RT-PCR检测IL-6、TNF和MMP-3 mRNA表达与对照组和非特异性siRNA组无显著差异。我们的研究结果表明，siHDAC1关节内电穿孔治疗的效果是通过诱导滑膜细胞凋亡而产生的抗增殖特性。

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.