实验性肾小管间质性肾炎免疫发病机理的探讨

Studies on the immunopathogenesis of experimental tubulointerstitial nephritis in Wistar rats

为探讨肾小管间质性肾炎的免疫发病机制，观察Ia抗原表达与肾小管间质性肾炎损害的关系，用兔肾小管基底膜（TBM）完全福氏佐剂及百白破疫苗，免疫雌性Wistar大鼠，成功地建立了肾小管间质性肾炎（TIN）模型。我们采用免疫组化和图像分析技术，研究TIN病变中单个核细胞的特征以及Ia抗原表达和TIN之间的关系。结果显示：在TIN发生时，TBM上有线型IgG沉积，这表明有抗TBM抗体产生。肾小管间质中渗出的单个核细胞，大多数为T细胞，部分有肉芽肿形成。B细胞逐渐减少，而单核细胞由少变多。肾间质损害表现为小管萎缩和间质纤维化。这些表明细胞免疫在TIN发病过程中起着重要作用。模型组中肾小管上皮细胞和Bowman囊Ia抗原表达强度比对照组高（P＜0．01），提示Ia抗原的表达可能影响TIN的发生和发展。

Tubulointerstitial nephritis (TIN) model was successfully induced in fernale Wistar ratsby immunization with rabbit tubular basement membrane (TBM) etc. By using immunohistochemistryand computerassisted image processing, characterization of mononuclear cells in the TIN rnodels weredetermined, and the re1ationship between Ia antigen expression of renal tissue and TIN studied. The re sults showed: TlN was characterized by deposition of IgG in a linear pattern along TBM and mononucle ar cells infiltrates, which suggests the production of anti-TBM antibodies. Among the mononuclearcells, most are T cells. Granuloma formation was observed in parts of TIN. B cells gradually decreasedwhile monocytes gradually increased. The renal tissue lesions show tubular atrophy and peritubular fi brosis. This model strong1y suggests that cellular immune responses play an important role in the devel opment of TIN. Ia antigen expression is higher in cells of the tubular epithelium and B0wman'S capsuleof lesion site than in control group (P<0.01). This is strong evidence that the abnormal expression ofIa antigen may be affected by the production and development of TIN.