二氧化硫对大鼠肢体缺血再灌注所致肺损伤的影响及其作用机制  

Role of sulfur dioxide in acute lung injury induced by ischemia-reperfusion of hind limbs in rats

作　　者：黄新莉[1] 周君琳[2] 黎宁[3] 范伯元[2] 

机构地区：[1]河北医科大学病理生理教研室,河北石家庄050017 [2]首都医科大学附属北京朝阳医院骨科,北京100020 [3]石家庄市第三医院骨科,河北石家庄050011

出　　处：《中国病理生理杂志》2013年第10期1747-1752,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81070050;No.30800440);北京市自然科学基金资助项目(No.7092035);河北省自然科学基金资助项目(No.C2008001040)

摘　　要：目的:探讨内、外源性二氧化硫(SO2)对肢体缺血再灌注(IR)所致大鼠急性肺损伤(ALI)的作用及其机制。方法:应用双大腿根部止血带复制大鼠双后肢IR后肺损伤模型。96只SD大鼠随机分为6组:假手术(sham)组、肢体缺血4 h再灌注4 h(IR)组、sham+SO2组、sham+异羟肟酸(hydroxamate,HDX)组、IR+SO2组和IR+HDX组。光镜下观察肺组织形态学改变并计数肺泡间隔中中性粒细胞(polymorphonuclear neutrophil,PMN)数目;测定肺系数和肺组织丙二醛(malondialdehyde,MDA)含量;测定肺内细胞间粘附分子(intercellular adhesion molecule,ICAM)-1以及血清肿瘤坏死因子(tumor necrosis factor,TNF)-α和白细胞介素(interleukin,IL)-1表达的变化;测定肺组织中SO2含量和天冬氨酸氨基转移酶(aspartate aminotransferase,AST)活性;观察动物24 h存活率。结果:大鼠肢体IR可引起肺组织出现损伤性变化,同时肺泡间隔中PMN数目、肺系数、肺组织MDA含量和ICAM-1水平以及血清TNF-α和IL-1含量增加,而肺组织SO2含量和AST活性下降、动物存活率降低;预先给予SO2供体Na2SO3/NaHSO3可明显减轻上述指标的变化;而预先给予体内SO2生成酶抑制剂HDX减少SO2的生成可加重IR所致的上述变化。结论:肺内AST/SO2体系下调参与介导了大鼠肢体IR致ALI的发生;外源性SO2通过抗炎、抗氧化发挥其改善肢体IR所致的肺损伤的作用。AIM：To explore the role of endogenous and exogenous sulfur dioxide（SO2） in acute lung injury（ALI） induced by ischemia-reperfusion（IR） of limbs in rats. METHODS：The rat model of ALI was induced by ischemia and reperfusion of the hind limbs using a tourniquet. The rats（n=96） were randomly divided into 6 groups： sham, IR, sham＋SO2, sham＋hydroxamate（HDX）, IR＋SO2 and IR＋HDX. The morphological changes of the lung tissues were observed under light microscope. Meanwhile, polymorphonuclear neutrophils（PMN） in alveolar septum, lung coefficient, lung levels of malondialdehyde（MDA） and intercellular adhesion molecule（ICAM）-1, serum tumor necrosis factor（TNF）-α and interleukin（IL）-1, the content of SO2 and the activity of aspartate aminotransferase（AST） in the lung tissues, and 24 h survival rate of the rats were measured. RESULTS：IR of the rat limbs resulted in the damage of the lung tissues, and the increases in PMN in alveolar septum, lung coefficient, the lung levels of MDA and ICAM-1 and the serum levels of TNF-α and IL-1 were also observed with the reductions of SO2 content and AST activity. Pretreatment with SO2 donor Na2SO3/NaHSO3 alleviated the changes of the indicators above. HDX, an inhibitor of SO2-producing enzymes, aggravated the changes above. CONCLUSION：Down-regulation of AST/SO2 pathway is involved in the pathogenesis of limb IR-induced ALI. Administration of exogenous SO2 might attenuate lung injury through anti-inflammation and anti-oxidation.

关 键 词：二氧化硫 急性肺损伤 再灌注损伤 

分 类 号：R363.2[医药卫生—病理学]