目的 明确明胶酶在弥漫增殖型狼疮肾炎中表达的变化及意义。方法 经过肾活检确诊的弥漫增殖型狼疮肾炎17例,分别进行基质金属蛋白酶(MMP)-2与MMP-9的免疫组织化学染色,并进行MMP-2与膜型基质金属蛋白酶(MT1-MMP)、MMP-9与CD68的免疫组织化学双重染色,平均治疗2.5年后行重复肾活检。观察其表达变化与疾病活动度、临床指标以及转归的关系。结果 正常对照组可有MMP-2的表达,但是少有MMP-9的表达。弥漫增殖型狼疮肾炎肾组织中MMP-2与MMP-9的表达明显增高,其中MMP-9的表达变化更为显著。MMP-2与MT1-MMP、MMP-9与CD68的表达密切相关。重复肾活检显示10例病情改善者MMP-2与MMP-9的表达分别下降了70%和62%。7例病情未缓解者表达仅下降了27%和32%。MMP-2与MMP-9的表达水平与狼疮肾炎病理活动性指数呈正相关。结论 明胶酶的表达与狼疮肾炎病理的活动性密切相关。
Objective To investigate the roles and significances of MMP-2 and MMP-9 in diffuse proliferative lupus nephritis by repeated renal biopsy. Methods Seventeen patients diagnosed by renal biopsy as WHO type Ⅳ lupus nephritis were analyzed by immunohistochemistry staining for MMP-2 and MMP-9. Double staining for MMP-2 and MT1-MMP, MMP-9 and CD68 were also performed. Patients had repeated renal biopsy after followed up for 2.5 years. The relationship between expressions of gelatinases and pathological activity index and clinical data were studied. Results MMP-2 immunoreactivity was detected in normal controls and was increased in diffuse proliferative lupus nephritis. MMP-9 staining, which was almost negative in normal glomeruli, was increased much more significantly in diffuse proliferative lupus nephritis. The immunoreactivity of MMP-2 and MMP-9 was positive in MT1-MMP staining and CD68-positive macrophages, respectively. The expression of MMP-2 and MMP-9 was reduced by 70% and 62% in 10 patients whose clinical condition was partially alleviated, while the expressions in 7 patients whose clinical condition was not alleviated, were only reduced by 27% and 32%. The staining for MMP-2 and MMP-9 were correlated with activity index of lupus nephritis and proteinuria. Conclusion Up-regulation of gelatinases expression in diffuse proliferate lupus nephritis is correlated to activity index of the disease.