【Animal modeling】-Effect of fibrinolytic system on podocyte injury in rats with membranous nephropathy

  Objective: To investigate the importance of early prevention of fibrinolytic disorder in preventing the progression of MN.

  Methods: The MN rat model was made according to the modified Border method, and the expression levels of uPA, tPA and PAI-1 in whole blood were detected at the 1st, 2nd, 3rd, and 4th weekends of formal immunization; the rat kidney tissue was collected to observe the kidney tissue with light microscope and electron microscope. Pathological changes; immunohistochemical methods were used to detect the protein expression levels of nephrin and WT1 in renal podocytes, and the correlation analysis was carried out.

  Results: Compared with the normal group and the intervention group, the whole blood uPA and tPA levels of the model group were significantly decreased, while the PAI-1 level was significantly increased, and the difference was statistically significant (P < 0.05). The foot processes of the ball podocytes were extensively fused to disappear; the GBM matrix appeared "spike-like protrusions", and the degree of renal interstitial fibrosis was severe. The expression of WT-1 and nephrin protein in the distribution area of glomerular podocytes was down-regulated, and the change of nephrin protein expression was statistically significant (P < 0.01). Correlation analysis showed that the levels of tPA and uPA in rat whole blood were positively correlated with the expression of nephrin protein in kidney tissue, and the level of PAI-1 in whole blood was negatively correlated with the expression of nephrin protein in renal tissue.

  Conclusion: In the development of MN, the fibrinolytic system plays an important role in podocyte injury and apoptosis. Early assessment and prediction of MN podocyte injury may find another therapeutic target for the prevention and treatment of early MN entering end-stage renal disease. Clinical research on drugs for the treatment of MN provides new ideas.