等毒性剂量芥子气不同途径诱导大鼠急性肺损伤的氧化应激反应差异探讨

Differential oxidative stress reactions in sulfur mustard-induced acute pulmonary injury with equal toxicity dose in rats via different routes

目的通过建立大鼠经腹腔和气管途径等毒性剂量(1LD50)芥子气(SM)急性肺损伤模型,比较2种肺损伤模型氧化应激反应的差异性。方法选取Sprague Dawley大鼠,随机分为腹腔SM组,腹腔丙二醇组,气管SM组,气管丙二醇组,正常组。采用酶联免疫吸附法和免疫组化法,检测血清酶和肺泡间隔相关蛋白表达。结果大鼠腹腔SM组血清各时间点超过氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)水平均高于同时点气管SM组(P<0.05);腹腔SM组肺泡间隔各时间点铜锌超过氧化物歧化酶(CuZn-SOD)、锰超过氧化物歧化酶(Mn-SOD)、对氧磷酶-1(PON-1)、载脂蛋白-1(ApoA1)表达的阳性细胞亦均高于气管SM组(P<0.05)。结论暴露SM(1LD50)后,2种大鼠急性肺损伤模型在分子水平氧化应激反应存在着差异性,提示等毒性剂量SM所致大鼠的氧化应激反应与染毒途径相关,并为抗氧化剂的应用提供了重要的理论依据。

Objective To compare oxidative stress responses of two acute pulmonary injury models induced by a toxicity dose (1LD50) of mustard gas (SM) in rats through intraperitoneal and tracheal pathways. Methods Male Sprague Dawley rats were selected and randomly divided into the intraperitoneal SM group, the intraperitoneal propylene glycol group, the tracheal SM group, the tracheal propylene glycol group and normal group. The serum enzyme levels and proteins related expressions in alveolar septum were measured by ELISA and immunohistochemistry methods. Results Serum levels of superoxide dismutase, catalase and glutathion peroxidase at different time points were increased in the intraperitoneal SM group compared with those of tracheal SM group (P<0.05). In the alveolar septum, the positive cells of CuZn-superoxide dismutase, Mn-superoxide dismutase, paraoxonase-1 and apolipoprotein-1 expression were increased in the intraperitoneal SM group compared with those of tracheal SM group (P<0.05). Conclusion At a dose of SM (1LD50), there are differences in the oxidative stress responses at the molecular level in two rat models of acute pulmonary injury. The results suggest that the oxidative stress responses reduced by equal toxicity dose (1LD50) of SM in rats are related to the toxic pathway, and which provides an important theoretical basis for the application of antioxidants.