络沙坦对大鼠急性坏死性胰腺炎肺损伤的保护作用

Losartan ameliorates acute pancreatitis-associated pulmonary injury

目的:研究络沙坦(Losartan)对急性坏死性胰腺炎(ANP)大鼠肺损伤的保护作用。方法:SD大鼠30只随机分为3组:正常对照组、ANP组、Losartan治疗组。采用大剂量精氨酸腹腔注射诱导ANP模型,治疗组于造模后30min给予Losartan200μg/kg,2次,每次间隔1h。各组于造模后24h处死大鼠,观察大鼠血浆血管紧张素Ⅱ(AngⅡ)、肾素(PRA)、淀粉酶(AMY)、TNF-α、IL-1β、肺组织髓过氧化物酶(MPO)、肺湿/干重比值、胰腺/体重比值、胰腺和肺组织病理变化。结果:ANP组血浆AngⅡ、PRA、AMY、TNF-α、IL-1β、MPO、肺湿/干重比值、胰腺/体重比值较对照组明显升高;Losartan治疗组血浆AngⅡ、PRA较ANP组变化不明显,AMY、TNF-α、IL-1β、MPO、肺湿/干重比值、胰腺/体重比值较ANP组明显下降,胰腺和肺组织病理损伤明显减轻。结论:络沙坦对血浆AngⅡ、PRA无明显影响,可以减少TNF-α、IL-1β、MPO的产生,对ANP肺损伤具有保护作用。

Objective： To investigate the therapeutic effect of losartan on acute necrotic pancreatltis-associated lung injury. Methods： 30 SD rats were divided into three groups randomly： control group, ANP group and losartan treatment group. The ANP model was induced by intraperitoneal injection of L arginine. The rats in losartan treatment group were injected losartan 200μg/kg twice per hour after the first administration of L arginine. The levels of angiotensin Ⅱ , renin, amylase, TNF-α, IL- β in blood, myeloperoxidase（MPO） in the lung, the wet/dry ratio of lung and the ratio of pancreatic weight to body weight were measured. Histopathological changes of lung and pancreas were also evaluated. Results： The levels of angiotensinⅡ , renin, amylase, TNF-α, IL- β,lung MPO, wet/dry ratio of lung and the ratio of pancreatic weight to body weight were increased in ANP group significantly compared with control group. Compared with the ANP group, the administration of losartan significantly reduced the levels of TNF-α, IL- β, lung MPO, wet/dry ratio of lung and the ratio of pancreatic weight to body weight, while not obvious change in the levels of angiotensin Ⅱ and rennin. Losartan also ameliorated the pancreas and lung histopathologic inflammation. Conclusion： Losartan ameliorates acute pancreatltis-associated pulmonary injury.