Flt-1、Flk-1在胶原诱导的关节炎小鼠关节组织中的表达

目的研究血管内皮生长因子(VEGF)受体F lt-1、F lk-1在Ⅱ型胶原诱导的关节炎(C IA)形成期的表达,探讨VEGF在类风湿性关节炎发病中的作用。方法于DBA/1 J小鼠皮下注射Ⅱ型胶原制作小鼠关节炎动物模型并进行关节指数评价,用ELISA法和免疫组织化学技术检测关节组织内VEGF及血管性假性血友病因子(vWF)含量,通过RT-PCR,Southern b lotting技术检测关节组织内VEGF及其特异性受体F lt-1、F lk-1mRNA表达。结果VEGF及vWF水平呈平行变化关系,均在关节炎发生后第四天达到最高水平,并与血管新生程度、关节炎严重程度呈正相关。关节组织内VEGF mRNA分别在279bp和304bp扩增片段有特异性表达、其特异性受体F lt-1、F lk-1 mRNA在377bp、402bp扩增片段有特异性表达。结论VEGF-F lt-F lk系统在关节炎形成早期起着重要作用,影响着实验诱导关节炎血管新生及病程。

Expression of Flt-1 and Flk-1 in Joint Tissue of Murine with Collagen-induced Arthritis

Objective To examine the expression and function of the angiogenic factor,vascular endothelial growth factor(VEGF) and the specific VEGF receptors(Flt-1and Flk-1) in the evolution of type Ⅱcollagen-induced arthritis(CIA),to explore the role of VEGF in the pathogenesis of rheumatic arthritis(RA).Methods Passive immunization was taken to induce CIA and arthritis index was evaluated.VEGF and von willebrand' s disease factor(vWF) proteins contents were measured by ELISA in articulation tissue,and their positive prpducts were visualized by immunohistochemistry.The expression of VEGF mRNA and two specific VEGF receptors,(Flt-1and Flk-1) mRNA were analyzed by RT-PCR and Southern blotting in the articulation tissue.Results The VEGF and vWF levels reached a maximum four days after the onset of arthritis and then gradually declined,correlated positively with neovascularization and footpat swelling.The specific expression fragments of VEGF mRNA were 279 bp and 304bp,those of Flt-1、Flk-1 mRNA were 377 bp and 402 bp respectively in arthritis joint tissues.Conclusion VEGF-Flt-Flk plays a crucial role in an early stage of arthritis development,affecting both neovascularization and the progress of exprimentally-induced sunovitis.