气体信号分子硫化氢对大鼠急性肺损伤的保护作用

目的 观察急性肺损伤(acute lung injury,ALI)时,内源性硫化氢(hydrogen sulfide,H2S)生成的变化以及应用外源性H2S后对ALI的影响.方法 Sprague-Dawley大鼠随机分为对照组、脂多糖(lipopolysaccharide,LPS)组、硫氢化钠(sodium hydrosulfide,NaHS)+LPS组以及NaHS+生理盐水(normal saline,NS)组(n均=12).LPS组大鼠每只气管内滴注LPS(100 μg/200 μl),对照组滴注等量NS.NaHS+LPS组大鼠滴注LPS前10 min腹腔注射NaHS(28 μmol/kg).各组均于滴注后4 h和8 h测定大鼠肺系数变化,光镜下观察肺组织形态学改变,检测肺组织中氧化性损伤产物丙二醛(malondialdehyde,MDA)含量以及支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中蛋白含量及中性粒细胞(polymorphonuclear neutrophil,PMN)计数的改变,并测定血浆中的H2S含量.结果 与对照组相比,LPS滴注4 h和8 h后,大鼠肺系数、肺组织中MDA含量、BALF中PMN数目及蛋白含量均明显升高(P值均＜0.01);而血浆中H2S含量则明显降低(P值均＜0.01);光镜下见肺泡萎陷、甚至结构消失,肺泡腔及间质弥漫性炎细胞浸润,部分肺泡代偿性气肿,且其病理改变随LPS滴注时间的延长而逐渐加重.与相应时间点的LPS组比较.NaHS+LPS组大鼠肺系数、肺组织中MDA含量、BALF中PMN数目及蛋白含量明显降低,血浆中H2S含量则明显升高(P值均＜0.01);光镜下肺间质和肺泡中炎细胞浸润程度明显减轻.结论 内源性H2S生成不足参与了ALI的形成过程,外源性H2S可以部分拮抗ALI,对肺组织起到细胞保护作用.

Protective effects of hydrogen sulfide on acute lung injury as a gasser transmitter

Objective To study the changes of endogenous hydrogen sulfide(H2S) in acute lung injury (ALI) and the effect of exogenous H2 S on ALI. Methods Male Sprague-Dawley rats were randomly divided into control group, lipopolysaccharide(LPS) group, sodium hydrosulfide (NaHS) + LPS group, NaHS + normal saline(NS) group(each n = 12). The rats in LPS group were instilled LPS (100 μg/200 μl) intra -tracheally,NS was instilled in control group. To rats of NaHS+ LPS group, Naris (28 μmol/kg) was injected intraperitoneally 10 min before LPS administration. Each parameter was observed respectively 4 h and 8 h after agent administration: the lung coefficient was measured; the change of lung tissue structure was observed using light microscope; malondialdehype (MDA) contents in the lung homogenate and polymorphonuelear neutrophil(PMN) number and protein content in bronehoalveolar lavage fluid (BALF) were detected;and blood from carotid artery was collected to detect H2S content. Results Compared with control group,the lung coefficient, MDA content in the lung and PMN number and protein content in BALF all increased 4 h and 8 h after LPS administration(all P ＜0.01). But H2S content of plasma decreased 4 h and 8 h after LPS administration(all P ＜ 0.01). The pathomorphological changes of lung tissues in LPS group expressed as diffuse infuse infiltration and migration of acute inflammation cells, accompanied by atrophied or damaged alveoli, and slight alveolar atelectasis or emphysema. Compared with the same time points of LPS group, the lung coefficient, MDA content in lung, PMN number and protein content in BALF decreased,but H2S content of plasma increased in NaHS+ LPS group (all P＜0. 05). The accumulation of inflammation cells in lung septa and alveoli also reduced after Naris applied. Conclusion Endogenous H2S was involved in the pathogenesis of rats' ALI. Exogenous H2S could exert protective effect during ALI.