类风湿关节炎中巨噬细胞移动抑制因子对内皮细胞功能及血管内皮生长因子的影响  

Macrophage migration inhibitory factor promotes proliferation of endothelial cell and increase expression of VEGF in Rheumatoid arthritis

作　　者：严瀚[1] 刘恩志[1] 周汉城[1] 钟波夫[1] 芦虎[1] 

机构地区：[1]广州市第一人民医院骨外科,510180

出　　处：《中华关节外科杂志（电子版）》2013年第3期67-70,共4页Chinese Journal of Joint Surgery(Electronic Edition)

基　　金：广东省科技计划项目(20120314)

摘　　要：目的探讨巨噬细胞移动抑制因子(MIF)对类风湿关节炎(RA)滑膜内皮血管生成的影响和作用机制。方法免疫组化检查MIF在RA滑膜组织中的表达;加入MIF或PBS溶液培养人微血管内皮细胞株(HMEC-1),CCK8法观察细胞的生长差异,磷脂酰丝氨酸凋亡试剂盒(AnnexinV法)检测细胞凋亡,RT-QPCR检测细胞中MIF及VEGF的表达差异。结果 MIF在5例RA组织中均阳性表达;加入MIF的细胞株增殖显著较加PBS溶液的快(F=216.93,P<0.01),细胞株的凋亡被MIF显著抑制(凋亡率从21.37%降为7.01%(t=13.88,P<0.01);处于分裂相的细胞数目较加入PBS的细胞株多(G2期+S期细胞比例从37.89%升为54.05%,t=5.42,P<0.01),在加入MIF的细胞株中VEGF的表达4.62倍高于加入PBS的细胞株(t=7.34,P<0.01)。结论 MIF在RA滑膜组织中表达,并通过提高血管内皮细胞的VEGF而促进RA滑膜血管生成而发挥重要的生理作用。MIF或许是治疗RA进展的药物靶点,有望通过抑制RA患者中MIF的表达从而延缓疾病的进展,改善患者的生活质量。Objective To study the effects of the macrophage migration inhibitory factor （MIF） on endothelial cells in rheumatoid arthritis （RA）, and to explore the mechanism of MIF in RA development. Methods lmmunohistoehemical staining was carried out to detect the expression of MIF in RA tissue. MIF or PBS was added to the culture medium of human microvascular endothelial cell line （ HMEC-1 ） respectively, then the cell proliferation and apoptosis were detected by CCK8 and Annexin V method respectively; the VEGF expresson in HMEC-1 was detected by RT-QPCR. Results MIF was positively expressed in cytoplasm of RA tissue. Compared to PBS control, MIF promoted the cell proliferation significantly （F = 216. 93 ,P 〈 0. 01 ）, decreased the apoptosis rate from 21.37% to 7. 01% （t = 13.88 ,P 〈0. 01 ）, improved the cell ratio of mitosis （the sum of G2-phase and S-phase arose from 37.89 to 54. 05% ） （t = 5.42, P 〈 0.01 ） , and significantly increased the VEGF expression to 4. 62 times （t = 7. 34,P 〈 0. 01 ）. Conclusions MIF expresses in RA tissues and may exert the important function through the endothelial cell. MIF may be a potential drug target for the treatment of RA progression, thereby it is expected to delay the progression of the disease, and improve the patient＇s life quality by inhibition of MIF expression in RA patients.

关 键 词：关节炎 类风湿 巨噬细胞游走抑制因子 内皮细胞 血管内皮生长因子类 

分 类 号：R593.22[医药卫生—内科学]