Reckelhoff J F, Kellum J A, Racusen L C, Hildebrandt D A
Department of Physiology, University of Mississippi Medical Center, Jackson 39216, USA.
Am J Physiol. 1997 Jun;272(6 Pt 2):R1768-74. doi: 10.1152/ajpregu.1997.272.6.R1768.
Aging is associated with loss of nephron function and reductions in serum L-arginine and excretion of nitric oxide (NO) metabolites. The present study was performed to determine if long-term dietary treatment with L-arginine, the NO synthase substrate, could prevent age-related renal injury. Studies were performed in four groups of rats, aged 12-13 mo, for 8 mo: group 1 received L-arginine (2% in 2.5% corn syrup, n = 5); group 2 received sodium nitrite, an NO donor (0.1%, in 2.5% syrup, n = 7); group 3 was an untreated control group (n = 7); group 4 was treated with 2.5% corn syrup (n = 5). Urinary protein increased and urinary nitrate/nitrite decreased with age in controls, but, during L-arginine treatment, urinary protein decreased and nitrate/nitrite increased. Two weeks after L-arginine was stopped, urinary protein had increased and nitrate/nitrite had decreased to the same level as in controls. L-Arginine treatment increased glomerular filtration rate (GFR) by 50% compared with untreated controls. In contrast, nitrite had no effect on GFR. Morphologically, L-arginine protected against aging injury by reducing the number of sclerotic glomeruli. In summary, we found that L-arginine prevented the age-related glomerular injury and reduction in GFR. The mechanism of protection, however, may be independent of NO.
衰老与肾单位功能丧失、血清L-精氨酸水平降低以及一氧化氮（NO）代谢产物排泄减少有关。本研究旨在确定长期用L-精氨酸（NO合酶底物）进行饮食治疗是否能预防与年龄相关的肾损伤。对四组12 - 13月龄的大鼠进行了为期8个月的研究：第1组给予L-精氨酸（在2.5%玉米糖浆中含2%，n = 5）；第2组给予亚硝酸钠，一种NO供体（在2.5%糖浆中含0.1%，n = 7）；第3组为未治疗的对照组（n = 7）；第4组用2.5%玉米糖浆治疗（n = 5）。对照组中，尿蛋白随年龄增加而增加，尿硝酸盐/亚硝酸盐随年龄减少，但在L-精氨酸治疗期间，尿蛋白减少，硝酸盐/亚硝酸盐增加。停止L-精氨酸治疗两周后，尿蛋白增加，硝酸盐/亚硝酸盐降至与对照组相同水平。与未治疗的对照组相比，L-精氨酸治疗使肾小球滤过率（GFR）提高了50%。相比之下，亚硝酸盐对GFR无影响。形态学上，L-精氨酸通过减少硬化肾小球的数量来预防衰老损伤。总之，我们发现L-精氨酸可预防与年龄相关的肾小球损伤和GFR降低。然而，保护机制可能与NO无关。
