硫化氢在脓毒症大鼠肺损伤中的作用

Effects of hydrogen sulfide on sepsis - induced lung injury

目的探讨硫化氢（H2S）在脓毒症大鼠肺损伤中的作用。方法雄性SD大鼠60只，随机分为4组：对照组（Ⅰ组）15只，脓毒症组（Ⅱ组）15只，脓毒症＋PAG（H：S代谢酶CSE抑制剂）组（Ⅲ组）15只，脓毒症＋NariS（H：S供体）预处理组（Ⅳ组）15只。采用盲肠结扎穿孔法制作脓毒症大鼠模型，观察各组动物的行为学特征，测定肺组织H2S浓度、肺组织CSEmRNA的表达、肺组织湿干重比（W／D）、肺组织MPO水平、肺组织TNF-α和IL-1β的表达，观察肺组织形态学改变。结果CLP模型组动物出现呼吸加快，与I组比较，Ⅱ组动物肺组织H2S、W／D、TNF—α、IL-1β水平明显升高（P〈0．01），MPO活性明显增加（P〈0．01），肺组织CSEmRNA的表达明显升高（P〈0．01）；与Ⅱ组比较，Ⅲ组动物呼吸频率接近，肺组织H2s、W／D、TNF-α、IL-1β水平明显降低（P〈0．01），MPO活性明显减弱（P〈0．01），肺组织CSEmRNA的表达明显降低（P〈0．01）；与Ⅱ组比较，Ⅳ组动物呼吸频率明显加快，少数出现呼吸衰竭，肺组织W／D、TNF-α、IL-113水平明显升高（P〈0．01），MPO活性明显增强（P〈0．01），肺组织CSEmRNA的表达有所降低，但差异无统计学意义（P〉0．05）；四组肺组织光镜下损伤由轻到重依次为：Ⅰ、Ⅲ、Ⅱ、Ⅳ。结论给予内源性H2S抑制剂可以使脓毒症大鼠肺组织W／D、TNF—α、IL-1β、MPO水平明显降低，减轻肺组织炎症及水肿损伤，给予外源性H2S可以加重肺炎症损伤。

Objective To investigate the effects of hydrogen sulfide（H2S） on sepsis -induced lung injury in rats. Methods 60 male SD rats were randomly divided into 4 groups： control group （ I group）, sepsis group （ II group）, sepsis ＋PAG （DL - propargylglycine） group （ III group）, sepsis ＋ NariS group （ IV group）. Cecal ligation and puncture （CLP）technique was used to make the rat models of sepsis in II , III, IV group. Behavioural characteristics were observed in all the groups. H2 S synthesis in lung tissues was detected. RT - PCR was used to assay CSE mRNA expression in lung in all the groups. The ratio of wet weight to dry weight （W/D） in lung tissue was measured. MPO assay kit was used to determine MPO activity of lung. The concentration of tumor necrosis -α （ TNF - α）, in terleukin - 1β （ IL - 1 β ） was detected by ELISA , and the morphological structure of lung were also observed. Results Compared with I group, respiratory rate of 11 group was increased significantly, wet lung appeared, and the W/D, the concentration of H2S, TNF -α, IL - 1β, the activity of MPO, CSE mRNA expression in lung were increased（P 〈 0.01 ）. Compared with 11 group, respiratory rate of III group was similar, H2S, the W/D, the concentration of TNF-α, IL- 1β and the activity of MPO, CSE mRNA expression in lung was decreased significantly （ P 〈 0.01 ）. Compared with I1 group , respiratory rate of group IVwas increased more significantly, a few showed respiratory failure, the W/D, the concentration of TNF-α, IL- 1β and the activity of MPO in lung was increased（ P 〈 0.01 ）, CSE mRNA expression in lung tissue decreased slightly （ P 〉 0.05 ）. Histomorphology injury of lung was gradually aggravated in the following order： I ,III, II, IV. Conclusion The inhibitor of endogenous H2S can decrease the level of W/D, MPO, TNF - α, IL - 1β and alleviate lung inflammatory and swelling injury. Oppositely, but exogenous H2S can aggravate it.