一氧化氮在实验性肾脏热缺血-再灌注损伤中的双相作用。

Biphasic role for nitric oxide in experimental renal warm ischaemia-reperfusion injury.

作者信息

Weight S C, Furness P N, Nicholson M L

机构信息

University Department of Surgery, Leicester General Hospital, Leicester LE5 4PW, UK.

出版信息

Br J Surg. 1999 Aug;86(8):1039-46. doi: 10.1046/j.1365-2168.1999.01162.x.

DOI:10.1046/j.1365-2168.1999.01162.x

PMID:10460640

Abstract

BACKGROUND

Whilst nitric oxide has a clearly defined role in renal haemostasis, debate continues over its pathophysiology. This study investigated the function of nitric oxide in a model of renal warm ischaemia-reperfusion injury.

METHODS

Rats underwent bilateral renal warm ischaemia (45 min) after pretreatment with nitric oxide donors, nitric oxide synthase (NOS) inhibitors or saline (control). Following reperfusion (20 min) a unilateral nephrectomy was performed to measure renal nitric oxide (as nitroxides) and oxidative DNA and protein damage. Renal function was measured on days 2 and 7 before terminal nephrectomy for analysis and morphology.

RESULTS

The increase in renal nitric oxide level seen early in reperfusion (20 min) (P < 0.01) was prevented by inhibition of constitutive (cNOS) but not inducible (iNOS) NOS. The increase in oxidative damage (P < 0.01) was exacerbated by nitric oxide donors (P < 0.01) but ameliorated by NOS inhibition (P < 0.01). Control nitric oxide remained increased through to day 7 (P < 0.01) but was reduced by nitric oxide donors and cNOS inhibitors (P < 0.05). Oxidative damage returned towards normal in the control group, whereas both DNA and protein damage persisted following NOS inhibition (P < 0.01).

CONCLUSION

Inhibition of the postischaemic increase in the level of nitric oxide was associated with an early decrease in, but eventual exacerbation of, oxidative damage. This suggests the prolonged increase in renal nitric oxide concentration was cytoprotective overall.

摘要

背景

虽然一氧化氮在肾止血中具有明确的作用，但其病理生理学仍存在争议。本研究在肾热缺血-再灌注损伤模型中研究了一氧化氮的功能。

方法

大鼠在分别用一氧化氮供体、一氧化氮合酶（NOS）抑制剂或生理盐水（对照）预处理后，进行双侧肾热缺血（45分钟）。再灌注（20分钟）后，进行单侧肾切除术，以测量肾一氧化氮（以氮氧化物形式）以及氧化性DNA和蛋白质损伤。在终末肾切除术前第2天和第7天测量肾功能，用于分析和形态学检查。

结果

再灌注早期（20分钟）观察到的肾一氧化氮水平升高（P<0.01）可通过抑制组成型（cNOS）而非诱导型（iNOS）NOS来预防。一氧化氮供体加剧了氧化性损伤的增加（P<0.01），但NOS抑制可改善这种情况（P<0.01）。对照组一氧化氮水平一直升高至第7天（P<0.01），但一氧化氮供体和cNOS抑制剂可使其降低（P<0.05）。对照组氧化性损伤恢复至正常，而NOS抑制后DNA和蛋白质损伤均持续存在（P<0.01）。