系统性红斑狼疮患者血清肝细胞生长因子及基质金属蛋白酶9的研究

Detection of Serum HGF and MMP-9 and Its Clinical Significance in Pat ients with Systemic Lupus Erythematosus

目的探讨血清肝细胞生长因子(HGF)及基质金属蛋白酶9(MMP-9)的水平与系统性红斑狼疮(SLE)疾病活动程度的关系和意义,并对相关机理进行探讨。方法①双抗体夹心法检测血清HGF及MMP-9水平;②绘制ECV304细胞株生长曲线;③明确重组人肝细胞生长因子(rhHGF)的作用浓度;④流式细胞仪检测MMP-9水平。结果患者血清HGF明显升高(P<0.001),MMP-9明显降低(P<0.001);经糖皮质激素治疗后HGF浓度下降(P<0.05),MMP-9浓度升高(P<0.05);活动期HGF高于非活动期(P<0.05),MMP-9低于非活动期(P<0.05);肾损组HGF高于非肾损组(P<0.001),MMP-9则低于非肾损组(P<0.05);关节炎组HGF高于非关节炎组(P<0.01),MMP-9水平两组之间差异无显著性(P>0.05);以HGF水平作为SLE的诊断指标,则ROC曲线下面积为0.707,灵敏度为66.7%;以MMP-9水平作为SLE的诊断指标,则ROC曲线下面积为0.984,灵敏度为97.2%;同时检测HGF及MMP-9水平,灵敏度为66.7%(24/36);rhHGF的作用浓度为8ng/mL;正常ECV304细胞株MMP-9的表达量为39.74%,rhHGF刺激后MMP-9的表达量为40.32%。结论HGF及MMP-9可能参与SLE的发病机制,其水平可作为反映疾病活动程度、肾脏损害以及疾病进展与改善的指标,且血清MMP-9水平诊断准确性更高;rhHGF可促进ECV304细胞株MMP-9的表达。

Objectives To explore the relationship between serum leve ls of hepatocyte growth factor (HGF) and matrix metalloproteinase-9 (MMP-9) and the disease activity of systemic lupus erythematosus (SLE), and study the mechan isms of these two factors in the pathogenesis of SLE. Methods The serum levels of HGF and MMP-9 were measured by ELISA. The growth curve of normal ECV304 cell line was obtained, and the action concentration of recombinant human hepatocyte growth factor (rhHGF) was determined. MMP-9 expression level in cells was detec ted by flow cytometric analysis. Results The serum level of HGF increased sign ificantly in SLE patients as compared with that in healthy controls (P < 0.001), but the serum level of MMP-9 decreased significantly (P < 0.001). The serum lev el of HGF decreased after treatment (P < 0.05), but MMP-9 increased (P < 0.05). The serum level of HGF was higher in patients with active disease than that in p atients with inactive disease (P < 0.05), but MMP-9 was lower (P < 0.05). The se rum level of HGF increased in patients with renal damage as compared with those without renal damage (P < 0.001), but the serum level of MMP-9 decreased (P < 0. 05). The serum level of HGF was higher in patients with arthritis than those wi thout (P < 0.01), but MMP-9 serum level had no significant difference in these t wo groups (P > 0.05). The area of ROC curve was 0.707 and the sensitivity was 66 .7% when using the serum level of HGF as diagnostic standard. The area under ROC curve was 0.984 and the sensitivity was 97.2% when using the serum level of MMP-9 as diagnostic standard. The sensitivity was 66.7% (24/36) when two markers (H GF and MMP-9) were examined simultaneously. Additionally, the action concentrati on of rhHGF was 8 ng/mL, and the expression level of MMP-9 was 39.74% in normal ECV304 cells and increased to 40.32% after rhHGF stimulation. Conclusions It i s suggested that HGF and MMP-9 may be involved in the pathogenesis of SLE, and s erum levels of HGF and MMP-9 might be used as markers for monitoring the disease activity, renal damage, disease progression and improvement in SLE. The sensiti vity might be higher when serum level of MMP-9 is used as diagnostic standard, a nd rhHGF can enhance MMP-9 expression in ECV304 cell line.