Department of General Surgery, Affiliated Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
Hum Exp Toxicol. 2010 Apr;29(4):329-37. doi: 10.1177/0960327110361760. Epub 2010 Feb 9.
To investigate the role of nitric oxide (NO) in acute lung inflammation and injury secondary to acute necrotizing pancreatitis (ANP), 5% sodium taurocholate was retrogradely injected into the biliopancreatic duct of rats to ANP model. These ANP rats were given L-Arginine (L-Arg, 100 mg/kg), L-NAME (10 mg/kg), or their combination by intraperitoneal injection 30 min prior to ANP induction. At 1, 3, 6, and 12 hours after ANP induction, lung NO production, and inducible NO synthase (iNOS) expression were measured. Lung histopathological changes, bronchoalveolar lavage (BAL) protein concentration, proinflammatory mediators tumor necrotic factor alpha (TNF-alpha), and lung tissue myeloperoxidase (MPO) activity were examined. Results showed that NO production and iNOS mRNA expression in alveolar macrophages (AMs) were significantly increased along with significant increases in lung histological abnormalities and BAL proteins in the ANP group, all of which were further enhanced by pretreatment with L-Arg and attenuated by pretreatment with L-NAME, respectively. These markers were slightly attenuated by pretreatment with combination of L-Arg + L-NAME, suggesting that NO is required for initiating the acute lung damage in ANP rats, and also that L-Arg-enhanced lung injury is mediated by its NO generation rather than its direct effect. MPO activity and TNF-alpha expression in lung were upregulated in the ANP rats and further enhanced by pretreatment with L-Arg and attenuated by pretreatment with L-NAME, respectively. These results suggest that overproduction of NO mediated by iNOS in the lung is required for the acute lung inflammation and damage secondary to ANP.
为了研究一氧化氮（NO）在急性坏死性胰腺炎（ANP）继发急性肺炎症和损伤中的作用，向大鼠的胆胰管逆行注射 5%牛磺胆酸钠以建立 ANP 模型。这些 ANP 大鼠在 ANP 诱导前 30 分钟通过腹腔内注射给予 L-精氨酸（L-Arg，100mg/kg）、L-NAME（10mg/kg）或它们的组合。在 ANP 诱导后 1、3、6 和 12 小时，测量肺 NO 产生和诱导型一氧化氮合酶（iNOS）表达。检查肺组织病理学变化、支气管肺泡灌洗液（BAL）蛋白浓度、促炎介质肿瘤坏死因子-α（TNF-α）和肺组织髓过氧化物酶（MPO）活性。结果表明，与 ANP 组相比，肺泡巨噬细胞（AMs）中的 NO 产生和 iNOS mRNA 表达显著增加，肺组织学异常和 BAL 蛋白显著增加，分别用 L-Arg 和 L-NAME 预处理可进一步增强和减弱这些标志物，提示 NO 是引发 ANP 大鼠急性肺损伤所必需的，并且 L-Arg 增强的肺损伤是通过其 NO 生成介导的，而不是其直接作用。肺 MPO 活性和 TNF-α表达在 ANP 大鼠中上调，并用 L-Arg 预处理进一步增强，并用 L-NAME 预处理减弱。这些结果表明，iNOS 在肺中产生的过量 NO 是继发于 ANP 的急性肺炎症和损伤所必需的。
