THE ROLE OF LIPIDS IN PROGRESSIVE RENAL INJURY

局灶性肾小球硬化(FGS)常见于人类和实验性肾小球硬化。 肾脏疾病的模型。典型的是，FGS伴随着 蛋白尿和肾功能进行性下降。尽管 FGS的发病机制尚未完全阐明，有几个 非免疫因素参与了这种疾病的发展。 损伤。有研究表明，肾小球毛细血管的增加 压力和流动可能是FGS发展的基础。 凝血、肾前列腺素代谢和系膜功能异常 肾小球大分子和肾小球上皮细胞的加工 细胞损伤可能也参与了FGS的发病机制。近期 我们实验室的研究表明，脂类代谢异常 可能是FGS发病的危险因素之一。我们已经证明了 两种截然不同的降脂剂，氯非匹酸和 梅维诺林显著改善5/6大鼠肾小球损伤 肾切除和肥胖的Zucker大鼠。这些研究的结果是 这让我们假设，血脂在糖尿病的发病机制中起着重要作用 FGS。此外，有可能在两国之间的协同作用 发病机制中可出现肾小球高血压和高脂血症。 FGS的作用方式类似于在较大的动脉粥样硬化中观察到的 血管。目前的研究旨在调查这一点。 肾小球血流动力学改变之间的协同作用， 例如肾小球性高血压，以及 FGS的发病机制。我们计划利用定义明确的实验 大鼠改变循环血脂和/或肾小球的药物 血流动力学。肾组织的显微穿刺术和组织学评价 以评估功能与结构的相关性。结果： 这些研究可能有助于更好地理解糖尿病的发病机制。 肾小球损伤，以及肾脏疾病患者的新方法 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.