TBM介导的肾间质纤维化中细胞外基质和金属蛋白酶的动态变化

Changes of extracellular matrix and metalloproteinases in TBM mediated tubulointerstitial fibrosis

目的 探讨实验性肾间质纤维化过程中 ,细胞外基质的变化规律以及金属蛋白酶和金属蛋白酶组织抑制剂的表达。方法 用TBM抗原、福氏完全佐剂和百白破疫苗免疫Wistar大鼠 ,诱导出自身免疫性肾小管间质性肾炎 (TIN)和肾间质纤维化 ,采用免疫组织化学方法观察不同时相细胞外基质 (fibronectin ,CollagenⅠ ,Ⅲ ,Ⅳ )的变化。结果 collagenⅣ和laminin沿着增厚的TBM增加 ,collagenⅠ和collagenⅢ在肾小管间质内 ,而fibronectin不仅存在于TBM上 ,而且存在于肾小管间质内。TIMP1从免疫后第 14d到第 2 1d逐渐在小管周的内皮和浸润的白细胞中表达增强 ;而MMP3 则表达减弱。结论 TBM介导的肾间质纤维化中细胞外基质逐渐增加 ,伴有TIMP的增加。

Objective To study change of extracellular matrix(ECM) ,tissue inhibitors of metalloproteinase(TIMP 1) and metalloproteinase (MMP 3) in autoimmune tubulointerstitial nephritis with tubulointerstitial fibrosis.Methods After autoimmune tubulointerstitial nephritis were induced by immunizing Wistar rats with rabbit TBM and complete freund's adjuvant, the expression of ECM(fibronectin, CollagenⅠ,Ⅲ,Ⅳ) and TIMP were detected with using immunohistochemistry and microscopy.Results CollagenⅣ and laminin increased along thickened TBM; collagenⅠand collagenⅢ were immunolocalized within the tubulointerstitium, while fibronectin was present in both the TBM and interstitium in rats with TIN on day 14.TIMP increased beginning on day 14 and persisted through day 21, while TIMP was immunolocalized within the peritubular endothelium and infiltrating leukocytes. In contrast, MMP3 reduced gradually.Conclusions These data suggest that ECM increase with an increase in TIMP in autoimmune tubulointerstitial nephritis.