Ingram A, Parbtani A, Thai K, Ly H, Shankland S J, Morrissey G, Scholey J W
Department of Medicine, University of Toronto, Ontario, Canada.
Kidney Int. 1995 Dec;48(6):1857-65. doi: 10.1038/ki.1995.484.
One effect of L-arginine is to increase nitric oxide (NO) production by endothelial cells. NO directly reduces endothelin-1 production by endothelial cells and also inhibits platelet-derived growth factor (PDGF) induced cell proliferation. Since subtotal renal ablation is associated with an early phase of cell proliferation in the glomerulus that precedes injury, we examined the effect of dietary supplementation with L-arginine on glomerular cell proliferation and expression of the cytokine endothelin-1 (ET-1). A first group of renal-ablated rats was untreated. A second group of renal-ablated rats received L-arginine (1%) in the drinking water. Two weeks after subtotal ablation renal cortical tissue was snap frozen for immunohistochemical analysis for proliferating cell nuclear antigen (PCNA) expression and ET-1. Protein and total RNA was extracted from sieved glomeruli. mRNA levels were quantitated by co-amplification RT-PCR utilizing specific 5' and 3' primers for rat ET-1 and beta-actin. L-arginine reduced the number of PCNA positive nuclei in remnant glomeruli, and Western blot Analysis of glomerular proteins also showed that L-arginine reduced PCNA expression. Glomerular ET-1 mRNA levels and protein immunostaining declined in the rats receiving L-arginine. We conclude that dietary supplementation with L-arginine reduces early cell proliferation in the remnant glomerulus, an effect that may be mediated, in part, by a decrease in ET-1 production.
L-精氨酸的一个作用是增加内皮细胞一氧化氮（NO）的生成。NO可直接减少内皮细胞内皮素-1的生成，还能抑制血小板衍生生长因子（PDGF）诱导的细胞增殖。由于肾次全切除与损伤前肾小球细胞增殖的早期阶段相关，我们研究了饮食中补充L-精氨酸对肾小球细胞增殖及细胞因子内皮素-1（ET-1）表达的影响。第一组肾切除大鼠未接受治疗。第二组肾切除大鼠饮用含1%L-精氨酸的水。肾次全切除两周后，将肾皮质组织速冻，用于增殖细胞核抗原（PCNA）表达和ET-1的免疫组化分析。从筛选后的肾小球中提取蛋白质和总RNA。利用大鼠ET-1和β-肌动蛋白的特异性5'和3'引物，通过共扩增逆转录聚合酶链反应（RT-PCR）对mRNA水平进行定量。L-精氨酸减少了残余肾小球中PCNA阳性细胞核的数量，对肾小球蛋白质的蛋白质印迹分析也显示L-精氨酸降低了PCNA的表达。接受L-精氨酸的大鼠肾小球ET-1 mRNA水平和蛋白质免疫染色均下降。我们得出结论，饮食中补充L-精氨酸可减少残余肾小球的早期细胞增殖，这一作用可能部分是由ET-1生成减少介导的。
