二氧化硫对脓毒症致急性肺损伤大鼠炎症反应的抑制作用  

Effect and mechanism of sulfur dioxide on inflammatory response in rats with acute lung injury induced by sepsis

作　　者：关岚[1] 刘志伟[1] 黄冬梅[1] 赵斌[1] Guan Lan;Liu Zhiwei;Huang Dongmei;Zhao Bin(Department of Emergency Medicine, Beijing Jishuitan Hospital, Beijing 100035, China)

机构地区：[1]北京积水潭医院急诊科,100035

出　　处：《北京医学》2018年第5期446-450,F0003,共6页Beijing Medical Journal

摘　　要：目的探讨二氧化硫(sulfur dioxide,SO_2)对盲肠结扎穿孔术(cecal ligation and puncture,CLP)诱导的脓毒症大鼠急性肺损伤炎症反应的作用及其机制。方法雄性SD大鼠32只随机分成4组,每组8只:假手术+生理盐水(Sham+NaCl)组,假手术+外源性SO_2供体Na_2SO_3/NaHSO_3(Sham+SO_2)组,盲肠结扎穿孔术+生理盐水(CLP+NaCl)组及盲肠结扎穿孔术+外源性SO_2供体Na_2SO_3/Na HSO3(CLP+SO_2)组。对各组大鼠肺组织显微镜下形态学观察,进行肺损伤半定量评分(index of quantitative assessment,IQA),测量肺湿干重比(wet/dry weight,W/D);采用酶联免疫吸附法(ELISA)检测肺组织中TNF-α、IL-6含量;采用蛋白质印迹法(Western blot)检测肺组织中NF-κB信号通路中磷酸化IκBα(p-IκBα)、IκBα、p-p65蛋白含量。结果光镜下,Sham+SO_2组与Sham+NaCl组相比,形态结构无明显变化;CLP+NaCl组肺组织明显变化,肺组织结构不完整,肺泡间隔明显增厚,肺间质以及肺泡水肿;与CLP+NaCl组相比,CLP+SO_2组肺泡结构较完整,肺泡间隔变窄,间质水肿减轻。与Sham+NaCl组相比,CLP+NaCl组大鼠IQA、W/D增加;与CLP+NaCl组相比,CLP+SO_2组大鼠IQA、W/D降低。与Sham+NaCl组相比,CLP+NaCl组大鼠肺组织中TNF-α、IL-6含量均升高;与CLP+NaCl组相比,CLP+SO_2组大鼠肺组织中TNF-α、IL-6含量均下降。与Sham+NaCl组相比,CLP+NaCl组大鼠肺组织中p-IκBα、p-p65的表达增强,IκBα的表达减弱;与CLP+NaCl组相比,CLP+SO_2组大鼠肺组织中p-IκBα、p-p65的表达减弱,IκBα的表达增强。结论 SO_2在脓毒症大鼠肺损伤中通过抑制炎性反应起保护作用,机制与抑制NF-κB信号通路有关。Objective To explore the effect and mechanism of sulfur dioxide（SO2） on inflammatory response in rats with acute lung injury induced by cecal ligation and puncture（CLP）. Methods Thirty-two male SD rats were randomly divided into four groups： the sham ＋ saline（Sham ＋ NaCl） group, sham ＋ SO2 donor Na2SO3/NaHSO3（Sham ＋ SO2）group, CLP＋saline（CLP＋NaCl） group, CLP＋SO2 donor Na2SO3/NaHSO3（CLP＋SO2） group. The lung morphology was observed. Index of quantitative assessment（IQA） of histological lung injury, lung wet/dry weight ratio（W/D） were calculated and the levels of TNF-α, IL-6 in lung tissue were measured by ELISA. The content of NF-κB signal transduction pathway, including phosphorylation of IκBα（p-IκBα）, IκBα and p-p65 protein in lung tissue, was detected by Western blot. Results Under microscope, in the Sham＋NaCl group, the lung morphology was normal, the alveolar wall was complete, there was no obvious secretion in alveolar cavity, no inflammatory cell infiltration and red blood cell infiltration.Compared with the Sham＋NaCl group, the sham＋SO2 group had similar morphological structure. There were significant changes in the lung tissue of the rats in the CLP＋NaCl group, the structure of the lung tissue was not complete, the alveolar septum was thickened, with pulmonary interstitial and alveolar edema. Compared with the CLP＋NaCl group, the CLP＋SO2 group had a more complete alveolar structure, narrow alveolar septum, and reduced interstitial edema. Compared with the Sham＋NaCl group, the IQA, W/D, levels of TNF-α, IL-6 in lung tissue in the CLP＋NaCl group were elevated and the expression of p-IκBα and p-p65 increased, and the IκBα expression decreased in lung tissue. Compared with the CLP＋NaCl group, the IQA, W/D, levels of TNF-α, IL-6 in lung tissue in the CLP＋SO2 group were decreased and the expression of p-IκBα and p-p65 was decreased either, while the IκBα expression was increased in lung tissue. Conclusion SO2 plays a prot

关 键 词：二氧化硫 脓毒症 急性肺损伤 炎性因子 核转录因子-ΚB 

分 类 号：R459.7[医药卫生—急诊医学] R563[医药卫生—治疗学]