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[血管活性肠肽基因重组质粒对大鼠胶原诱导性关节炎的实验性治疗]

[Experiment treatment of collagen-induced arthritis in rats with recombinant plasmid containing vasoactive intestinal peptide gene].

作者信息

Zhang Li-qun, Shen Jian-gen

机构信息

Institute of Immunology, College of Medicine, Zhejiang University, Hangzhou 310031, China.

出版信息

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2006 Jul;35(4):403-10. doi: 10.3785/j.issn.1008-9292.2006.04.011.

DOI:10.3785/j.issn.1008-9292.2006.04.011
PMID:16924705
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-alpha, 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.

RESULT

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-alpha, 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-alpha and IL-2 levels of pcDNA3.1+/VIP-treated 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.

摘要

目的

探讨含血管活性肠肽基因的重组质粒（pcDNA3.1+/VIP）对大鼠胶原诱导性关节炎（CIA）的治疗作用。

方法

采用在雄性SD大鼠皮内注射弗氏佐剂乳化的牛Ⅱ型胶原诱导实验性关节炎。然后给大鼠关节腔内注射重组质粒（pcDNA3.1+/VIP）。采用抗生物素蛋白-生物素过氧化物酶复合物-酶联免疫吸附测定法（ABC-ELISA）检测血清肿瘤坏死因子-α（TNF-α）、白细胞介素-4（IL-4）和白细胞介素-2（IL-2）水平，并观察大鼠关节的病理变化。

结果

组织学检查显示关节内有大量炎性浸润，伴有骨和软骨破坏，而经VIP处理的大鼠滑膜病理变化的严重程度明显减轻。与正常组相比，CIA大鼠血清TNF-α、IL-2水平显著升高（P<0.05），IL-4水平降低（P<0.05）。与对照组和经pcDNA3.1+处理的CIA大鼠相比，经pcDNA3.1+/VIP处理的大鼠血清TNF-α和IL-2水平降低，IL-4水平升高（P<0.05）。

结论

含血管活性肠肽基因的重组质粒（pcDNA3.1+/VIP）可减轻已建立的CIA的临床和组织学严重程度，可能是类风湿关节炎治疗的一个有前景的候选药物。

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