【作者】 周晓红；

【导师】 凌亦凌；

【作者基本信息】 河北医科大学 ， 病理学与病理生理学， 2006， 博士

【摘要】 急性肺损伤(acute lung injury,ALI)是多种原因引起的,以肺泡毛细血管膜和肺上皮广泛受损所致的肺水肿和肺不张为主要特征,临床上可表现为呼吸窘迫和顽固性低氧血症,进一步发展即为急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)。多种病因(包括肺内/肺外,感染/非感染)都能直接或间接地引起ALI及ARDS。革兰氏阴性细菌内毒素的主要活性成分脂多糖(lipopolysaccharide,LPS)是导致肺部感染和全身感染的主要因素。LPS由其受体介导启动机体炎症反应,进而导致全身性炎症反应综合征(systemic inflammatory response syndrome,SIRS),在肺部可表现为ALI。LPS所致ALI是以中性粒细胞(polymorphonuclear neutrophil,PMN)浸润为主的肺组织炎症反应,PMN在肺内的大量扣押、激活及释放大量炎症介质及活性氧物质等,导致弥漫性肺组织损伤,是其发病学的中心环节。然而对于LPS启动机体炎症反应、导致ALI的具体机制尚未完全阐明。内源性气体信号分子是一类具有多种病理生理作用的生物物质,它们的发现为ALI发病机制的研究开辟了一个新的领域。迄今已证实的内源性气体信号分子有三种,即一氧化氮(nitric oxide, NO)、一氧化碳(carbon monoxide, CO)和硫化氢(hydrogen sulfide, H2S)。NO和CO在ALI中的作用已得到了证实。H2S是继NO和CO之后被确认的第三种内源性气体信号分子。关于生理和病理情况下H2S作用的研究虽刚刚起步,但已证实H2S参与了神经和血管等的生理功能调节,以及高血压、肺动脉高压、内毒素休克等疾病的发生。那么,探明H2S在LPS所致ALI中发挥何种作用,是本研究的主要目的之一。内源性气体信号分子之间存在着相互调节的关系。已有研究证实NO与CO之间可对彼此产生的限速酶进行调节。而关于ALI时NO与H2S之间相互关系如何,尚未见相关报道。有研究报道气体信号分子NO可参与生理状态下肺功能的调节和多更多还原

【Abstract】 Acute lung injury (ALI), is mainly characterized by diffusive injuries to lung epithelium and increased permeability of alveolar-capillary membranes caused by various factors, which lead to pulmonary edema and pulmonary closure. It expresses as distress of respiratory and refractory hypoximia clinically. There are many etiological factors that can evoke ALI/ARDS directly or indirectly. Lipopolysaccharide (LPS), the main component of the cell wall of gram-negative bacteria, is one of the most important factors causing pulmonary infection and systemic infection. LPS plays an important role in initiating inflammatory response through binding to its receptors and causing systemic inflammatory response syndrome (SIRS) which can induce ALI. ALI induced by LPS is an acute pulmonary inflammation response in the lung, in which the accumulation and activation of polymophonuclear neutrophil (PMN) and the release of a large number of inflammatory mediators and oxygen free radical are the key link. However, it remains incompletely illuminated the definite mechanism of LPS initiating inflammatory over-reaction and inducing ALI.Endogenous gaseous transmitters, a unique class of biomaterials in regulating homeostasis, are found to play important roles in a variety of physiological and pathological events. Up to now, three gaseous transmitters have been recognized, namely nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S). Mounting evidence confirmed the important role of NO and CO in ALI. H2S is the third to be included in the family of endogenous gaseous transmitters, following NO and CO. Researches about physiological functions and pathological effects of H2S became frequent only recently. It was proved that H2S participated in the regulation of neural function and vasomotion, as well as the pathogenesis of hypertension,更多还原