芥子气经腹腔和气管致大鼠ALI模型氧化应激反应的机制

Mechanism of oxidative stress reaction due to sulfur mustard-induced acute lung injury in rats via intraperitoneal and tracheal injection

目的经腹腔和气管建立大鼠芥子气（sulfur mustard，SM）ALI动物模型，比较2种大鼠ALI模型氧化应激反应的差异。方法选取SpragueDawley大鼠136只，随机分为5组，正常对照组8只，其他4个组（腹腔SM组、腹腔丙二醇组、气管SM组、气管丙二醇组）每组32只。腹腔SM组腹腔内注入稀释的SM0．1ml（0．96LD50=8mg／kg），气管SM组气管内注入稀释的SM0．1ml（0．98LD50=2mg／kg），正常对照组不做任何处理。采用酶联免疫吸附试验和免疫组化，判断氧化应激情况。结果腹腔SM组各时间段BALF中乳酸脱氢酶、谷胱甘肽过氧化物酶水平均高于气管SM组（P值均〈0．05）。腹腔SM组各时间段血清γ-谷氨酰转肽酶、硫代巴比妥酸反应产物水平均高于气管SM组（P值均〈0．05）。腹腔SM组大鼠肺组织各时间段肺泡间隔8=羟基脱氧鸟苷阳性细胞表达率、红系衍生的核因子2相关因子2和血红素氧合酶1蛋白阳性表达率均高于气管SM组（P值均〈0．05）。结论大鼠在经腹腔和气管SM浓度相似的情况下，经腹腔途径肺氧化应激指标与经气管相比显著升高，推测可能与腹腔对SM的快速吸收有关。

Objective To establish animal model of sulfur mustard （SM）-induced acute lung injury in rats via intraperitoneai and tracheal injection, in order to compare the difference of oxidative stress reaction. Methods 136 male Sprague Dawley rats were selected and randomly divided into five groups, the control group with eight cases, other four groups （i. e. the intraperitoneal SM group, the intraperitoneal propylene glycol group, the tracheal SM group, the tracheal propylene glycol group） with 32 cases in each group. The rats in intraperitoneal SM group were injected intraperitoneally with diluted SM 0.1 ml （0.96 LD50 = 8 mg/kg）, the rats in tracheal SM group were injected intratracheally with diluted SM 0.1 ml （0.98 LD50=2 mg/kg）, meanwhile the status quo was kept with the normal group. SM-induced oxidative stress was-observed by enzyme linked immunosorbent assay and immunohistochemical staining. Results In bronchoalveolar lavage fluid, lactate dehydrogenase and glutathione peroxidase levels in the intraperitoneal SM group at a period of time were increased compared with the tracheal SM group （all P〈 0.05）. Serum T-glutamyl transpeptidase and thobarbituric acid reactive substances levels in the intraperitoneal SM group at a period of time were higher than those in the tracheal SM group （all P〈0.05）. In the alveolar septum, the positive expression ratios of γ-hydroxy deoxyguanosine, nuclear factor- E2 related factor 2 and heme oxygenase-1 in the intraperitoneal SM group at a period of time were increased compared with the tracheal SM group （all P 〈0.05）.Conclusions Under similar concentration of SM via intraperitoneal and tracheal injection in rats, indexes of lung oxidative stress in the intraperitoneal injection are increased compared with the tracheal injection, which may be related to fast absorption of the peritoneal cavity to SM.