Weight S C, Furness P N, Nicholson M L
University Department of Surgery, Leicester General Hospital, UK.
Br J Surg. 1998 Dec;85(12):1663-8. doi: 10.1046/j.1365-2168.1998.00960.x.
Nitric oxide has a clearly defined place in normal renal homoeostasis while there is a continuing debate as to its role under pathophysiological conditions. This study investigated the role of nitric oxide in a model of renal warm ischaemia-reperfusion injury.
Groups of rats underwent bilateral renal warm ischaemia (for 15-60 min) followed by reperfusion (20 or 80 min) before unilateral nephrectomy for measurement of renal nitric oxide (as nitroxides) and oxidative damage. Renal function was measured on days 2 and 7 before killing and nephrectomy. A further group received the nitric oxide synthase inhibitor N(G)-nitro L-arginine methyl ester (L-NAME; 50 mg per kg body-weight) before induction of warm ischaemia.
In early reperfusion there was a correlation between the duration of warm ischaemia (15-45 min) and renal nitrate (r2=0.97) which increased from a mean(s.e.m.) baseline value of 95(5.9) to 208(17.3) nmol per mg protein following 45 min of warm ischaemia. Levels were further raised at 80 min and maintained through to day 7 (241(12.5) nmol per mg protein in 45-min group). This rise was attenuated by L-NAME (P< 0.01) as was the early rise in oxidative damage seen otherwise. By day 7, however, oxidative damage was increased (all P< or = 0.01).
Renal nitric oxide increased early in recoverable warm ischaemia-reperfusion injury and remained raised to day 7. Nitric oxide synthase inhibition ameliorated early but exacerbated late damage suggesting that the early burst of nitric oxide is cytotoxic but that overall nitric oxide may exert a cytoprotective effect.
一氧化氮在正常肾脏稳态中具有明确的作用，但其在病理生理条件下的作用仍存在持续争论。本研究调查了一氧化氮在肾脏热缺血再灌注损伤模型中的作用。
将大鼠分组，在单侧肾切除术前进行双侧肾脏热缺血（15 - 60分钟），随后再灌注（20或80分钟），以测量肾脏一氧化氮（以亚硝酸盐形式）和氧化损伤。在处死和肾切除术前第2天和第7天测量肾功能。另一组在热缺血诱导前接受一氧化氮合酶抑制剂N(G)-硝基-L-精氨酸甲酯（L-NAME；50毫克/千克体重）。
在早期再灌注时，热缺血持续时间（15 - 45分钟）与肾脏硝酸盐之间存在相关性（r2 = 0.97），热缺血45分钟后，其从平均（标准误）基线值95（5.9）升高至208（17.3）纳摩尔/毫克蛋白。80分钟时水平进一步升高，并维持至第7天（45分钟组为241（12.5）纳摩尔/毫克蛋白）。L-NAME可减轻这种升高（P < 0.01），否则早期氧化损伤的升高也会减轻。然而，到第7天，氧化损伤增加（所有P ≤ 0.01）。
在可恢复的热缺血再灌注损伤早期，肾脏一氧化氮增加，并持续升高至第7天。一氧化氮合酶抑制可改善早期损伤，但会加重晚期损伤，表明早期一氧化氮爆发具有细胞毒性，但总体上一氧化氮可能发挥细胞保护作用。
