乌司他丁对百草枯诱导急性肺损伤的保护作用研究

摘要

Objectives To establish rats model of acute lung injury by paraquat and study the protective effect of ulinastatin ( UTI) against paraquat( PQ)-induced acute lung injury( ALI) and its mechanism.Methods All 45 healthy adult Wister rats were randomizedly assigned into three groups:normal control group,PQ group,UTI group.①NS group( n=5):the same volume of 0.9%saline solution was orally administered to rats.②PQ group( n=20):20% paraquat(30mg/kg) was given by the oral cavity at the first day.③UTI group( n=20):ulinastatin (100 000u/kg) was injected into peritoneum at 30 minutes after oral administration of PQ.The content of maleic dialdehyde ( MDA) ,glutathione peroxidase( GSH-Px) and superoxide dismutase( SOD) activity in blood and bronchoalveolarlavage fluid(BALF)were routinely measured at the times of 8,24,48 and 72h respectively.Results ①Com-pared with control group,the level of MDA in PQ group increased significantly both in plasma and BALF(P<0.01);SOD and GSH-Px in plasma were all decreased (P<0.01).The activities of SOD and GSH-Px in BALF were all decreased,but SOD showed in-crease 48h later(P<0.01).②Compared UTI group with PQ group,the MDA level decreased both in plasma and BALF(P<0.05), the SOD and GSH-Px activities were significantly increased as well(P<0.01).Conclusions Ulinastatin alleviates paraquat(PQ)-induced acute lung injury in rats,which may be attributed to its attenuation of lipid peroxidation in the tissues.%目的：通过建立百草枯中毒急性肺损伤大鼠模型，探讨乌司他丁（ UTI）对百草枯（ PQ）致急性肺损伤（ ALI）的保护作用及可能机制。方法将健康Wister大鼠45只随机分为三组：对照组、PQ组、UTI组。对照组：腹腔注入生理盐水；PQ组：给予含百草枯（30mg／kg）的溶液经胃管注入；UTI组：百草枯染毒后30分钟腹腔注入含乌司他丁（100000u／kg）的等容量生理盐水。每组取8小时、24小时、48小时、72小时共4个观察点，测定血液及BALF中丙二醛（ MDA）的含量、谷胱甘肽过氧化物酶（ GSH－Px）和超氧化物歧化酶（ SOD）活性。结果①PQ中毒组与对照组比较：中毒组血浆和BALF中MDA含量显著高于对照组，差异有显著性（ P＜0．01）；血浆SOD活力GSH－Px均下降，差异有显著性（ P＜0．01）；BALF中SOD、GSH－Px活力均下降，但48小时后SOD升高，差异有显著性（P＜0．01）。②UTI治疗组与PQ中毒组比较：给予UTI治疗后的治疗组与中毒组比较，血浆中MDA含量明显下降（P＜0．01），BALF中MDA含量下降（P＜0．05）；GSH－Px和SOD活力升高，差异有显著性（ P＜0．01）。结论 UTI对PQ中毒大鼠急性肺损伤具有保护作用，机制可能是减轻了肺组织的脂质过氧化反应。