Paczek L, Teschner M, Schaefer R M, Heidland A
Department of Medicine, Medical University Würzburg, FRG.
Diabetologia. 1991 Nov;34(11):786-9. doi: 10.1007/BF00408351.
The obese Zucker rat is a classic model of non-immune mediated spontaneous focal glomerulosclerosis. An important initiating hallmark of glomerulosclerosis in this model is mesangial matrix expansion. Fibronectin, a highly biologically active glycoprotein, is a normal constituent of mesangial extracellular matrix. Using a quantitative method based on enzyme immunoassay we assessed the intraglomerular fibronectin content and its degradation in obese Zucker rats and their lean littermates. In the obese Zucker rats the glomerular fibronectin content was significantly higher in comparison to the controls (88 +/- 6 vs 48 +/- 4 ng/10(3) glomeruli). Furthermore, proteinase activity against fibronectin was significantly reduced in the glomeruli of obese Zucker rats when compared to control animals (at pH 5.4: 186 +/- 6 U/mg protein vs 286 +/- 14 U/mg protein, at pH 7.4: 152 +/- 12 U/mg protein vs 193 +/- 12 U/mg protein). These data demonstrate that in obese Zucker rats there is a glomerular accumulation of fibronectin which we propose is at least partly due to diminished proteolytic digestion. Whether accumulation of intraglomerular fibronectin contributes to progressive glomerulosclerosis remains a matter of debate.
肥胖型 Zucker 大鼠是一种非免疫介导的自发性局灶性肾小球硬化的经典模型。该模型中肾小球硬化的一个重要起始标志是系膜基质扩张。纤连蛋白是一种具有高度生物活性的糖蛋白，是系膜细胞外基质的正常组成成分。我们采用基于酶免疫测定的定量方法，评估了肥胖型 Zucker 大鼠及其瘦型同窝仔鼠肾小球内纤连蛋白的含量及其降解情况。与对照组相比，肥胖型 Zucker 大鼠的肾小球纤连蛋白含量显著更高（88±6 对 48±4 ng/10³个肾小球）。此外，与对照动物相比，肥胖型 Zucker 大鼠肾小球中针对纤连蛋白的蛋白酶活性显著降低（在 pH 5.4 时：186±6 U/mg 蛋白对 286±14 U/mg 蛋白，在 pH 7.4 时：152±12 U/mg 蛋白对 193±12 U/mg 蛋白）。这些数据表明，在肥胖型 Zucker 大鼠中存在纤连蛋白在肾小球内的蓄积，我们认为这至少部分是由于蛋白水解消化减少所致。肾小球内纤连蛋白的蓄积是否会导致进行性肾小球硬化仍存在争议。
