Diamond J R, Karnovsky M J
Ren Physiol. 1986;9(6):366-74. doi: 10.1159/000173102.
Aminonucleoside nephrosis progresses over an 18-week period to focal and segmental glomerulosclerosis (FSGS). Whole heparin has been shown to blunt the extent of renal injury in another model of FSGS, renal ablation; however, the precise mechanism of protection has remained uncertain. Since heparin has a variety of physiologic actions unrelated to anticoagulation, we administered three different heparin compounds, each with a distinct profile of biological properties, to groups of rats given a single intravenous dose of puromycin aminonucleoside (PA). In the absence of a prolongation of the activated partial thromboplastin time (aPTT), both whole heparin (WH) and a 7,000- to 11,000-dalton-molecular-weight nonanticoagulant heparin (NAH) ameliorated the functional and histologic abnormalities of chronic aminonucleoside nephrosis as evidenced by significant reductions in 24-hour urine protein excretion while preserving the glomerular filtration rate and blunting the rise in serum creatinine as compared to untreated PA control animals at the conclusion of the study. In addition, the NAH and WH groups exhibited significantly fewer glomeruli with either segmental mesangial proliferative areas or glomerulosclerosis/hyalinosis lesions 18 weeks after PA administration. A fragment of heparin (HF) was ineffective. We conclude that heparin may exert its beneficial effect in chronic aminonucleoside nephrosis through a biologic action, other than anticoagulation, perhaps by inhibition of mesangial cell proliferation.
氨基核苷肾病在18周内进展为局灶节段性肾小球硬化（FSGS）。在FSGS的另一种模型——肾切除模型中，已证明全肝素可减轻肾损伤的程度；然而，其确切的保护机制仍不清楚。由于肝素具有多种与抗凝无关的生理作用，我们给单次静脉注射嘌呤霉素氨基核苷（PA）的大鼠组施用了三种不同的肝素化合物，每种化合物具有独特的生物学特性。在活化部分凝血活酶时间（aPTT）未延长的情况下，全肝素（WH）和分子量为7000至11000道尔顿的非抗凝肝素（NAH）均改善了慢性氨基核苷肾病的功能和组织学异常，这表现为24小时尿蛋白排泄显著减少，同时与研究结束时未治疗的PA对照动物相比，肾小球滤过率得以保留，血清肌酐升高得到缓解。此外，在PA给药18周后，NAH组和WH组中出现节段性系膜增生区域或肾小球硬化/玻璃样变病变的肾小球明显较少。一种肝素片段（HF）无效。我们得出结论，肝素可能通过抗凝以外的生物学作用在慢性氨基核苷肾病中发挥有益作用，可能是通过抑制系膜细胞增殖。
