THE ROLE OF LIPIDS IN PROGRESSIVE RENAL INJURY

局灶性肾小球硬化症（FGS）是常见于人类和实验性肾小球硬化症。 肾脏疾病的模型。 典型地，FGS伴随着 蛋白尿和肾功能进行性下降。 虽然 FGS的发病机制尚未得到精确阐明，一些 非免疫因素也参与了这一过程。 损伤。 有人认为，肾小球毛细血管增加， 压力和流量可能是FGS发展的基础。 抑制凝血、肾前列腺素代谢和系膜细胞增殖 致炎大分子以及肾小球上皮细胞的加工 细胞损伤也可能参与FGS的发病机制。 最近 我们实验室的研究表明，脂质代谢异常 可能是FGS发病的危险因素。 我们已经证明 两种明显不同的降脂剂，氯贝酸和 mevinolin，显着改善肾小球损伤的大鼠5/6 肾切除术和肥胖Zucker大鼠。 这些研究的结果 使我们假设脂质在糖尿病的发病机制中是重要的， FGS。 此外，可能的是， 发病机制中可能存在肾小球高血压和高脂血症 与在动脉粥样硬化中观察到的类似， 血管 本研究旨在探讨这一点 提出了肾小球血流动力学改变之间的协同作用， 例如，在一个实施例中，肾小球高血压和脂质代谢异常 FGS的发病机制。 我们计划利用定义明确的实验 在大鼠中改变循环脂质和/或肾小球 血流动力学 肾组织的显微穿刺和组织学评价将 以评估功能-结构相关性。 结果 这些研究可能有助于更好地了解 肾小球损伤，以及肾脏病患者的新方法 疾病

Focal glomerulosclerosis (FGS) is commonly seen in human and experimental models of renal disease. Characteristically, FGS is accompanied by proteinuria and a progressive decline in renal function. Although the pathogenesis of FGS has not been precisely illucidated, several non-immunologic factors have been implicated in the development of this lesion. It has been suggested that increased glomerular capillary pressures and flows may be fundamental to the development of FGS. Abnormalities in coagulation, renal prostaglandin metabolism and mesangial processing of phlogogenic macromolecules as well as glomerular epithelial cell damage may also participate in the pathogenesis of FGS. Recent studies from our laboratory have indicated that abnormal lipid metabolism may be a risk factor in the pathogenesis of FGS. We have demonstrated that two distinctly different lipid-lowering agents, clofibric acid and mevinolin, significantly ameliorated glomerular injury in rats with 5/6 nephrectomy and in obese Zucker rats. The results of these studies have led us to postulate that lipids are an important in the pathogenesis of FGS. Moreover, it is possible that a synergistic interaction between glomerular hypertension and hyperlipidemia could occur in the pathogenesis of FGS in a manner analogous to that observed in atherosclerosis of larger blood vessels. The present studies are designed to investigate this proposed synergistic interaction between altered glomerular hemodynamics, e.g., glomerular hypertension, and abnormal lipid metabolism in the pathogenesis of FGS. We plan to utilize well defined experimental manuevers in rats to alter circulating lipids and/or glomerular hemodynamics. Micropuncture and histologic evaluation of renal tissue will be performed to assess functional-structural correlations. Results of these studies may lead to a better understanding of the pathogenesis of glomerular injury, as well as to new approaches for patients with renal diseases.