低分子量肝素延缓进行性肾小球硬化的实验研究

摘要

Objective: This article was to study the effect and mechanism oflow-molecular weight heparin（LMWH）on ameliorating progressive glomerulosclerosis. Methods: The progressive glomerulosclerosis models were established by repeated injection of adriamycin to the rats after the removal of their right kidneys. The therapeutic group was received the treatment of LMWH for six weeks. The proteinuria, blood-biochemistric, and renal pathologic lesion were investigated respectively; the sclerotic index of glomerulus were calculated and the expression of collagen IV(Col-IV), laminin, platelet-derived growth factor B(PDGF-B) and basic fibroblast growth factor(bFGF) in glomerulus were determined by immunohistochemistry simultaneously. Results: LMWH not only reduced the proteinuria, elevated the serum albumin, improved the renal function, alleviated the renal pathologic lesion, and reduced the sclerotic index of glomerulus, but also significantly decreased the accumulation of Col-IV and laminin and the expression of PDGF-B and bFGF in glomerulus. Conclusion: LMWH may obviously ameliorate the progressive glomerulosclerosis; the decreased accumulation of mesangial matrix by inhibiting the expression of PDGF-B and bFGF in glomerulus may be one of the important mechanisms.%目的：探讨低分子量肝素（LMWH）对进行性肾小球硬化的延缓作用及可能机制。方法：通过摘除右肾后重复注射阿霉素的方法建立进行性肾小球硬化大鼠模型，给予LMWH治疗6周，观察大鼠蛋白尿、血生化及肾脏病理改变，计算肾小球硬化指数，运用免疫组织化学法检测肾小球Ⅳ型胶原蛋白（Col-Ⅳ）、层粘蛋白、血小板源性生长因子-B（PDGF-B）及碱性成纤维细胞生长因子（bFGF）的表达。结果：LMWH治疗后，进行性肾小球硬化大鼠的尿蛋白排泄明显降低，血清白蛋白升高，肾功能得以改善，肾脏病理改变减轻，肾小球硬化指数下降，Col-Ⅳ和层粘蛋白在肾小球系膜区的积聚减少，PDGF-B和bFGF在肾小球的表达受到抑制。结论：LMWH能明显延缓进行性肾小球硬化，其作用与抑制肾小球PDGF-B和bFGF的蛋白表达从而减少肾小球系膜基质的积聚有关。