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重组血管活性肠肽基因质粒治疗大鼠胶原性关节炎的研究
Experiment treatment of collagen-induced arthritis in rats with recombinant plasmid containing vasoactive intestinal peptide gene
【摘要】 目的:观察重组血管活性肠肽(pcDNA 3.1+/V IP)质粒治疗胶原诱导的大鼠关节炎(C IA)对血清TNFα-、IL-2、IL-4表达的影响和病理变化,探讨V IP基因治疗类风湿性关节炎的效果及可能机制。方法:以Ⅱ型胶原诱导的大鼠关节炎作为C IA模型,重组血管活性肠肽质粒关节腔内注射治疗C IA,以双抗体夹心酶联免疫吸附法(ABC-EL ISA)检测血清TNFα-、IL-2和IL-4的表达,观察病理变化和整体疗效。结果:①病理切片显示C IA模型组炎性细胞浸润明显,并存在骨和软骨破坏,V IP治疗组可显著减轻关节炎性病理改变;②细胞因子测定显示:与正常组相比,各对照组血清TNFα-、IL-2水平显著升高(P<0.05),IL-4水平减低(P<0.05);与各对照组相比,各重组V IP质粒治疗组血清TNF-α和IL-2表达水平均明显降低(P<0.05),IL-4表达则升高(P<0.05)。结论:血管活性肠肽基因质粒关节腔内注射治疗大鼠C IA具有显著的疗效,有望成为RA的有效治疗手段。
【Abstract】 Objective: To investigate the therapeutical effect of recombinant plasmid containing vasoactive intestinal peptide gene(pcDNA3.1+/VIP) on collagen-induced arthritis(CIA) in rats.Methods: The experimental arthritis was induced by intradermal injection of bovine type Ⅱ collagen emulsified in Freund’s adjuvants in male SD rats.The rats then were given intra-articular injection with recombinant plasmid(pcDNA3.1+/VIP).The levels of serum TNF-α,IL-4 and IL(-2) were detected by Avidin-Biotin Peroxdase Complex-enzyme-linked immunosorbent assay(ABC(-ELISA)) and the pathological changes in the joint of rats were observed.Results: Histological examination showed massive inflammatory infiltration in the joint with destruction of bone and cartilage,while the severity of pathological changes in synovia of VIP-treated rats was markedly reduced.Compared with normal group,the serum TNF-α,IL-2 levels of CIA rats were significantly increased(P<0.05) and IL-4 level was decreased(P<0.05).Compared with control and pcDNA3.1+-treated CIA rats,serum TNF-α and IL-2 levels of pcDNA3.1+/VIP-teated rats were decreased and IL-4 level was increased(P<0.05).Conclusion: Recombinant plasmid containing vasoactive intestinal peptide gene (pcDNA3.1+/VIP) can reduce the clinical and histological severity of established CIA and it might be a promising candidate for treatment of rheumatoid arthritis.
【Key words】 Arthritis,rheumatoid/pathol; Arthritis,experimental; Vocative intestinal peptide/ther use; Collagen type Ⅱ; Gene therapy;
- 【文献出处】 浙江大学学报(医学版) ,Journal of Zhejiang University(Medical Sciences) , 编辑部邮箱 ,2006年04期
- 【分类号】R593.22
- 【被引频次】6
- 【下载频次】101