血清血管内皮生长因子及可溶性血管内皮生长因子受体1在系统性红斑狼疮患者中的表达及其意义

The expression and significance of vascular endothelial growth factor and its soluble receptor sFlt-1 in the serum of patients with systemic lupus erythematosus

目的研究血清中血管内皮生长因子（VEGF）及可溶性血管内皮生长因子受体1（sFit-1）在活动期系统性红斑狼疮（SLE）及不同肾脏病理类型的狼疮肾炎（LN）患者中表达的意义。方法采用双抗体夹心酶联免疫吸附法（ELISA）对60例SLE患者及30名健康人血清中VEGF及sFlt-1的水平同时进行检测，结合临床资料及肾脏病理进行相关分析。结果活动期SLE患者血清VEGF及sFit-1水平均明显升高；血清中VEGF/sFlt-1的比值健康对照组较活动期SLE、非活动期SLE及LN组患者降低（P〈0．01），V型LN组该比值较Ⅱ、Ⅲ、Ⅳ型LN组升高（P〈0．05）；血清sFit-1的浓度与尿蛋白呈正相关（rs=0．6244，P〈0．01），血清VEGF的浓度与尿蛋白无明显相关（f0．1807，P〉0．05）；血清sFlt-1的浓度与ESR正相关（rs=0．4235，P〈0．01），血清VEGF的浓度与ESR无明显相关（rs=0．0532，19〉0．05）；血清VEGF及sFlt-1浓度与SLE疾病活动指数（SLEDAI）均呈正相关（q=0．5046，P〈0．01，F0．5152，P〈0．01）；血清VEGF浓度与肾组织活动指数（RAI）呈正相关（q=0．3386，P〈0．05），血清sFlt-1浓度与RAI无明显相关（q=0．0240，P〉0．05）；SEE患者中VEGF、sFlt-1水平与血压、血肌酐、尿素氮、C3、C4、C反应蛋白（CRP）无明显相关。结论血清VEGF及sFlt-1的水平可作为SLE病情活动评价指标，VEGF的高表达可能与增殖性肾小球病变相关，slit-1的表达与蛋白尿关系密切。

Objective To investigate the serum concentration of vascular endothelial growth factor （VEGF） and its soluble receptor 1 （sFlt-1） in patients with systemic lupus erythematosus （SLE） and its correlation with clinic and pathologic parameters. Methods serum levels of VEGF and sFlt-1 in a group of 60 patients with SLE and 30 healthy controls were assessed by ELISA. Results The VEGF and sFlt-1 serum levels were higher in active SLE group than the control group （P〈0.01）. The VEGF/sFlt-1 ratio in the control group was lower than that in the active SLE group, inactive SLE group and LN group （P〈0.01）. Particularly the ratio increased in WHO class V LN group compared to WHO class Ⅱ ,Ⅲ , Ⅳ LN group （P〈0.05）. The serum level of sFlt-1 was correlated to proteinuria（rs=0.6244, P〈0.01 ）and ESR（rs=0.4235, P〈0.01 ） and the serum levels of VEGF and sFlt-1 were correlated to the systemic lupus erythematosus disease activation index （SLEDAI） （rs=0.5046, P〈0.01 and rs=0.5152, P〈0.01, respectively）. The serum level of VEGF was correlated with renal tissue activation index （RAI） （rs=0.3386, P〈0.05） and the serum levels of VEGF and sFl5-I were not correlated to blood pressure, serum creatine, blood ureanitrogen, C3, C4, C-reative protein. The multi-factors stepwise regression analysis indicated that serum VEGF was positively correlated with SLEDAI （R2=0.175, P〈0.05）, serum sFlt-1 was positively correlated with ESR and proteinurine （R2=0.497, P〈0.05）. Conclusion Serum VEGF and sFlt-1 are elevated in patients with active SLE and they can reflect the activity of the disease. The overexpression of serum VEGF might be correlated to the proliferated glomerulonephritis and the overexpression of sFh-1 contribhtes to proteinuria. The imbalance between these two factors may act an important role in SLE pathogenesis.