关键词: &alpha, -胞衬蛋白 , 小干扰RNA, 非肥胖糖尿病, 白细胞介素4, 干扰素&gamma, 干燥综合征

Abstract: Abstract:Objective To observe the effects of α-Fodrin siRNA on the  expressions of IFN-γ and IL-4 of Sjogren’s syndrome (SS)  model non-obese diabetic (NOD) mice and to discuss its possibility  on treatment of NOD. Methods 12 female NOD mice were randomly divided into control group (n=3),empty vector group (n=3),α-Fodrin siRNA1 group (n=3),and α-Fodrin siRNA2 group (n=3). The vectors expressing α-Fodrin and  siRNA  1 and  α-Fodrin siRNA2 were injected by tail vein into NOD mice in α-Fodrin siRNA1 group and α-Fodrin siRNA2 group,while the  NOD mice in control group and empty vector group were injected with the same dose of PBS and pGFP-V-RS empty vector,respectively. The water drinking amount of each mouse was detected in each week.The expression levels of IFN-γ and IL-4 in serum of the mice in various groups were detected by ELISA method on the 1st,3rd,5th,and 7th day after injection,and the expression levels of α-Fodrin mRNA in lung tissue of NOD mice were detected by RT-PCR method and the expression level of α-Fodrin protein was detected by immunohistochemistry method.Results There were no significant differences of water drinking amounts of the mice between four groups(P>0.05).The levels of IL-4 were higher and IFN-γ/IL-4 ratios were lower in siRNA1 group and siRNA2 group than control group and empty vector group on the 1st and 3rd day after injection (P<0.05);the levels of IL-4 and IFN-γ/IL-4 in control group and empty vector group had no  significant differences on the 1st and 3rd day after injection;so did α-Fodrin siRNA1 group and α-Fodrin siRNA2 group. There were no significant differences  of the levels of IL-4 and the ratios of IFN-γ/IL-4 between various groups on the 5th and the 7th day. The expression levels of α-Fodrin mRNA and protein were lower in siRNA1 group and siRNA2 group than control group and empty vector group on the 7th day after injection (P<0.05);the expression levels of α-Fodrin protein were lower in siRNA1 group and siRNA2 than control group and empty vector group on the 7th day after injection (P<0.05);the expression levels of α-Fodrin mRNA and protein in control group and empty vector group had no significant differences;the expression levels of α-Fodrin mRNA and protein in siRNA1 group and siRNA2 group had  no   significant difference on the 7th day after injection. Conclusion α-Fodrin siRNA can elevate the expression of IL-4 and suppress the expression levels of α-fodrin mRNA and protein,at the same time,it can decrease the ratios of IFN-γ/IL-4;α-Fodrin siRNA could reduce the levels of inflammatory cytokines of NOD mice and delay  the development of SS.

Key words: &alpha, -Fodrin protein, small interfering RNA, non-obese diabetic, interleukin-4, interferon -&gamma, Sjogren&rsquo, s syndrome