【摘要】 目的:观察脂多糖(LPS)所致内毒素性急性肺损伤(ALI)大鼠肺泡表面活性物质(PS)的变化及硫化氢(H2S)对PS的影响,探讨H2S对肺脏的作用机制。方法:雄性SD大鼠共48只,随机分为6组(n=8):空白对照组、LPS组、LPS+NaHS低、中、高剂量组、LPS+PPG组。空白对照组给予生理盐水,LPS组给予LPS,LPS+NaHS低、中、高剂量组和LPS+PPG组分别在给予LPS 3 h时腹腔注射低、中、高剂量氢硫化钠(NaHS)或炔丙基甘氨酸(PPG)。各组均于给予生理盐水或LPS 6 h时电镜下观察肺泡Ⅱ型上皮细胞(AEC-Ⅱ)的形态改变,检测血浆中H2S含量、肺组织中胱硫醚-γ-裂解酶(CSE)活性、肺泡灌洗液(BALF)中总蛋白(TP)和总磷脂(TPL)含量、及肺组织中肺泡表面活性蛋白A、B、C(SP-A、B、C)mRNA表达的变化。结果:①与空白对照组比较,LPS组AEC-Ⅱ超微结构明显受损,血浆中H2S含量、肺组织中CSE活性、BALF中TPL的含量、及肺组织中SP-A、B、CmRNA表达均明显降低(P<0.05,P<0.01),BALF中TP的含量明显增加(P<0.01);②与LPS组比较,LPS+NaHS低、中、高剂量组,AEC-Ⅱ超微结构均有所恢复,血浆中H2S含量、肺组织中CSE活性、SP-AmRNA表达均明显升高(P<0.05,P<0.01);LPS+NaHS中、高剂量组BALF中TPL含量明显增高,SP-BmRNA表达升高(P<0.05);LPS+NaHS高剂量组BALF中TP含量明显降低(P<0.05);LPS+NaHS各剂量组SP-CmRNA表达无明显变化;③与LPS组比较,LPS+PPG组AEC-Ⅱ超微结构仍损伤严重,血浆中H2S含量、肺组织中CSE活性、BALF中TPL的含量、及肺组织中SP-A、B、CmRNA表达均明显降低(P<0.05),BALF中TP的含量明显升高(P<0.05)。结论:PS降低是内毒素性ALI的重要病理生理过程,H2S对LPS诱导的ALI有保护性作用,其机制可能与H2S对PS的调节有关。更多还原

【Abstract】 Objective: To observe the changes of pulmonary surfactant(PS) in rats with acute lung injury(ALI) induced by lipopolysaccharide(LPS) and to explore the effects of hydrogen sulfide(H2S) on PS.Methods: Fourtyeight male rats were randomly divided into six groups(n=8).They were control group,LPS group,LPS+ NaHS low,middle,high dose groups and LPS+ PPG group.Saline was admi-nistrated in Control group.LPS was administrated in LPS group.In LPS+ NaHS low, middle,high dose groups or LPS+ PPG group,sodium hydrosulfide(NaHS) of different doses or DL-propargylglycine(PPG) were respectively administrated when the rats were administrated of LPS after 3 hours.All the rats were killed at 6 hours after administration of Saline or LPS.The morphological changes of alveolar epithelial type Ⅱcells(AEC-Ⅱ) were respectively observed by transmission electron microscopes.The content of H2S in plasma and activity of cystathionine-γ-lyase(CSE) in lung tissues were respectively detected.The contents of total protein(TP) and total phospholipids(TPL) in bronchoalveolar lavage fluid(BLAF) were respectively measured.The pulmonary surfactant protein A(SP-A),surfactant protein B(SP-B) and surfactant protein-C(SP-C) mRNA expressions in lung tissues were analysed.Results: ①Compared with control group,the content of H2S in plasma,activity of CSE,content of TPL,and SP-A,SP-B and SP-C mRNA expressions were respectively decreased in LPS group(P<0.05 or P<0.01).But the content of TP was increased in LPS group(P<0.01);②Compared with LPS group,the content of H2S,activity of CSE and SP-A mRNA expression were significantly increased in LPS+NaHS low,middle and high dose groups(P<0.05).The SP-B mRNA expression and content of TPL were significantly increased in LPS+ NaHS Middle and High dose groups(P<0.05).The content of TP was decreased in LPS+ NaHS High dose group(P<0.05).The SP-C mRNA expression was not altered in LPS+NaHS low,middle and high dose groups(P>0.05);③Compared with LPS group,the content of H2S,activity of CSE,content of TPL,and SP-A,SP-B and SP-C mRNA expressions were respectively decreased,but content of TP was increased in LPS+ PPG group(P<0.05).Conclusion: The decrease of PS is the important physiopathologic process of ALI induced by LPS.Exogenously applied H2S could attenuate the process of ALI that possibly because H2S could adjust the compose and secretion of PS.更多还原