Narita I, Border W A, Ketteler M, Ruoslahti E, Noble N A
Division of Nephrology, University of Utah School of Medicine, Salt Lake City 84132, USA.
Proc Natl Acad Sci U S A. 1995 May 9;92(10):4552-6. doi: 10.1073/pnas.92.10.4552.
We have previously shown beneficial effects of dietary protein restriction on transforming growth factor beta (TGF-beta) expression and glomerular matrix accumulation in experimental glomerulonephritis. We hypothesized that these effects result from restriction of dietary L-arginine intake. Arginine is a precursor for three pathways, the products of which are involved in tissue injury and repair: nitric oxide, an effector molecule in inflammatory and immunological tissue injury; polyamines, which are required for DNA synthesis and cell growth; and proline, which is required for collagen production. Rats were fed six isocaloric diets differing in L-arginine and/or total protein content, starting immediately after induction of glomerulonephritis by injection of an antibody reactive to glomerular mesangial cells. Mesangial cell lysis and monocyte/macrophage infiltration did not differ with diet. However, restriction of dietary L-arginine intake, even when total protein intake was normal, resulted in decreased proteinuria, decreased expression of TGF-beta 1 mRNA and TGF-beta 1 protein, and decreased production and deposition of matrix components. L-Arginine, but not D-arginine, supplementation to low protein diets reversed these effects. These results implicate arginine as a key component in the beneficial effects of low protein diet.
我们先前已表明，饮食蛋白质限制对实验性肾小球肾炎中转化生长因子β（TGF-β）表达及肾小球基质积聚具有有益作用。我们推测这些作用源于饮食中L-精氨酸摄入量的限制。精氨酸是三条途径的前体，其产物参与组织损伤与修复：一氧化氮，炎症和免疫组织损伤中的效应分子；多胺，DNA合成和细胞生长所必需；以及脯氨酸，胶原蛋白产生所必需。大鼠在通过注射对肾小球系膜细胞有反应的抗体诱导肾小球肾炎后立即开始喂食六种等热量饮食，这些饮食在L-精氨酸和/或总蛋白含量上有所不同。系膜细胞溶解和单核细胞/巨噬细胞浸润在不同饮食组间并无差异。然而，即使总蛋白摄入量正常，饮食中L-精氨酸摄入量的限制仍导致蛋白尿减少、TGF-β1 mRNA和TGF-β1蛋白表达降低，以及基质成分的产生和沉积减少。向低蛋白饮食中补充L-精氨酸而非D-精氨酸可逆转这些作用。这些结果表明精氨酸是低蛋白饮食有益作用的关键成分。
