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

作　　者：张利群[1] 沈建根[1] 

机构地区：[1]浙江大学医学院免疫研究所,浙江杭州310031

出　　处：《浙江大学学报（医学版）》2006年第4期403-410,共8页Journal of Zhejiang University(Medical Sciences)

基　　金：国家自然科学基金项目(30170874);浙江省教育厅科研基金项目(20040232)

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。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 mtradermal 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.

关 键 词：关节炎 类风湿/病理学 关节炎 实验性 血管活性肠肽/治疗应用 胶原Ⅱ型 基因疗法 

分 类 号：R593.22[医药卫生—内科学]