Abstract:

[Abstract]   Objective   To investigate the therapeutic effect of tumor necrosis factor (TNF)-αsiRNA on typeⅡ colla?
gen induced arthritis (CIA) in rats.  Methods   The expression vectors of siRNA against TNF-αgene were constructed successfully and were injected by tail veil into CIA rats. Twenty-four CIA rats were randomly divided into4groups including model group, empty vector group, TNF-α-siRNA1group and TNF-α-siRNA2group. CIA rats were injected with the same dose of phosphate buffered sodium (PBS) and pGFP-V-RS vector respectively in model group and empty vector group, while TNF-α-siRNA1group and TNF-α-siRNA2group were injected with TNF-α-siRNA1eukaryotic expression vector andTNF-α-siRNA2eukaryotic expression vector respectively. Another6rats, which were not established CIA model, were in-jected with PBS (blank control group). The serum expression levels of IL-1were detected by ELISA on day1, 5, 9and13after injection. The expression level of TNF-αmRNA was detected by reverse transcriptase polymerase chain reaction (RTPCR) on day13.   Results   The expression level of IL-1was significantly higher on day1, 5, 9and13in model group than that of blank group (P<0.05). The expression levels of IL-1were significantly lower on day1, 5and9in TNF-α-siRNA1group and TNF-α- siRNA2group than that of model group and blank group (P<0.05). The expression level of TNF-αmRNA was significantly higher on day13in model group than that of blank group (P<0.05). The expression levels of TNF-αmRNA were significantly lower in TNF-α-siRNA1group and TNF-α-siRNA2group than those of model group and empty vector group (P<0.05).   Conclusion   TNF-αspecific siRNA can suppress the levels of TNF-αmRNA and IL-1, which provides experimental basis for gene therapy of rheumatoid arthritis.

Key words: tumor necrosis factor-α, RNA, Small interfering, interleukin-1, arthritis, experimental, disease models, 动物