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

我们采用体内电穿孔的方法检测了靶向组蛋白脱乙酰基酶1(SiHDAC1)的siRNA的治疗效果。关节内注射siHDAC不影响抗胶原抗体诱导的小鼠关节炎的红肿或足爪肿胀。然而，与对照组和非特异性siRNA组相比，siHDAC1治疗组的滑膜增生、骨侵蚀和关节软骨变性程度较轻。TUNEL染色显示siHADC组滑膜组织中阳性细胞数增多。经siHDAC处理后，关节滑膜成纤维细胞中HDAC1的表达降低，而RT-PCR检测到的IL-6、肿瘤坏死因子和基质金属蛋白酶-3mRNA的表达与对照组和非特异性siRNA组相比无显著差异。我们的结果提示，关节腔内电穿孔siHDAC1的治疗作用是通过诱导滑膜细胞凋亡而产生的抗增殖作用。

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.