二烯丙基三硫对脂多糖诱导急性肺损伤小鼠的防治作用及其机制研究
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摘要
目的:急性肺损伤(acute lung injury,ALI)和急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)是指心源性以外各种肺内外致病因素(严重感染、创伤、休克等)导致的急性、进行性、顽固性呼吸衰竭。失控性炎症反应引发多器官功能障碍综合症(multiple organ dysfunction syndrome,MODS)的理论强调了ALI/ARDS的本质是全身炎症反应综合征(systemic inflammatory response syndrome,SIRS)和MODS的肺部表现。ALI和ARDS是性质相同但程度不同的连续病理生理过程,ALI是ARDS的早期阶段,严重的ALI被定义为ARDS。ALI/ARDS发病急,病情凶险,尽管机械通气等治疗方法的综合应用,但至今无特效的治疗方法,病死率仍高达40～60%。
脓毒症(sepsis),特别是革兰氏阴性杆菌内毒素是导致ALI/ARDS最常见的原因。脂多糖(lipopolysaccharide,LPS)是内毒素的主要成份,是动物ALI/ARDS模型最常用的致伤剂。因此,注射LPS不仅可成功复制ALI/ARDS动物模型,而且可以很好地模拟临床严重感染引发的ALI/ARDS。LPS主要通过激活多种炎性细胞或效应细胞(中性粒细胞、巨噬细胞等),诱生大量细胞因子和炎症介质(如TNF-α、IL-1β、IL-6、PAF等)的失控性释放,从而引起肺泡毛细血管内皮和肺泡上皮损伤,肺微血管通透性增高,肺水肿及透明膜形成。因此参与炎症反应的炎性细胞,炎性细胞释放的细胞因子、炎症介质及相应的信号转导在ALI/ARDS的发生、发展中起关键作用,是形成ALI/ARDS的病理生理学基础。二烯丙基三硫(diallyl trisulfide,DATS)是大蒜提取物的主要成分。大蒜为百合科葱属植物生蒜(Allium satirum. L)的鳞茎,其中DATS和二烯丙基二硫化物(diallyl disulfide,DADS)在大蒜提取物中含量最高,是大蒜提取物的主要有效活性成分。现代医学证实:大蒜提取物具有广谱抗菌消炎作用,对于细菌及深部真菌感染均有一定的治疗效果。新近德国慕尼黑大学药物研究中心Keiss等报道,大蒜提取物可抑制LPS诱导的人全血细胞核
Objective: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) has been defined as acute, progressive, stubborn respiratory failure with refractory hypoxemia induced by different non-cardiogenic predisposing factors, such as sepsis, trauma and shock. These are most likely to result in multiple organ dysfunction syndrome (MODS). ALI/ARDS has been considered as pulmonary component of systemic inflammatory response syndrome (SIRS) and MODS based on the theory that MODS is induced by excessive inflammation. The pathophysiological pathogenesis of ALI and ARDS is similar, but ARDS is the severe endpoint of ALI. No specific therapy can cure ALI/ARDS, although mechanical ventilation and other methods have been conducted. The desease is devastating in clinic patients and the reported mortality for the dissease ranges from 40% to 60%.
Sepsis, especially endotoxin released by Gram-negative bacteria, is the main cause of ALI/ARDS. Lipopololysaccharide (LPS), the main outer membrane component of endotoxin of Gram-negative bacteria, is the most common reagent to duplicate ALI/ARDS model which is similar to ALI/ARDS patients induced by severe infection in clinic. Inflammation and related effector cells, such as neutrophil and macrophage is actived by stimulating with LPS. Uncontrolled release of multiple inflammatory mediators and cytokines including TNF-α, IL-1β, IL-6, PAF have been considered to contribute to the injury of microvascular endothelium and alveolar epithelium. As a result, vascular permeability increases which results in the formation of pulmonary edema, hyaline membrane and interstitial fibrosis. Therefore inflammation and related effector cells, inflammatory
脓毒症(sepsis),特别是革兰氏阴性杆菌内毒素是导致ALI/ARDS最常见的原因。脂多糖(lipopolysaccharide,LPS)是内毒素的主要成份,是动物ALI/ARDS模型最常用的致伤剂。因此,注射LPS不仅可成功复制ALI/ARDS动物模型,而且可以很好地模拟临床严重感染引发的ALI/ARDS。LPS主要通过激活多种炎性细胞或效应细胞(中性粒细胞、巨噬细胞等),诱生大量细胞因子和炎症介质(如TNF-α、IL-1β、IL-6、PAF等)的失控性释放,从而引起肺泡毛细血管内皮和肺泡上皮损伤,肺微血管通透性增高,肺水肿及透明膜形成。因此参与炎症反应的炎性细胞,炎性细胞释放的细胞因子、炎症介质及相应的信号转导在ALI/ARDS的发生、发展中起关键作用,是形成ALI/ARDS的病理生理学基础。二烯丙基三硫(diallyl trisulfide,DATS)是大蒜提取物的主要成分。大蒜为百合科葱属植物生蒜(Allium satirum. L)的鳞茎,其中DATS和二烯丙基二硫化物(diallyl disulfide,DADS)在大蒜提取物中含量最高,是大蒜提取物的主要有效活性成分。现代医学证实:大蒜提取物具有广谱抗菌消炎作用,对于细菌及深部真菌感染均有一定的治疗效果。新近德国慕尼黑大学药物研究中心Keiss等报道,大蒜提取物可抑制LPS诱导的人全血细胞核
Objective: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) has been defined as acute, progressive, stubborn respiratory failure with refractory hypoxemia induced by different non-cardiogenic predisposing factors, such as sepsis, trauma and shock. These are most likely to result in multiple organ dysfunction syndrome (MODS). ALI/ARDS has been considered as pulmonary component of systemic inflammatory response syndrome (SIRS) and MODS based on the theory that MODS is induced by excessive inflammation. The pathophysiological pathogenesis of ALI and ARDS is similar, but ARDS is the severe endpoint of ALI. No specific therapy can cure ALI/ARDS, although mechanical ventilation and other methods have been conducted. The desease is devastating in clinic patients and the reported mortality for the dissease ranges from 40% to 60%.
Sepsis, especially endotoxin released by Gram-negative bacteria, is the main cause of ALI/ARDS. Lipopololysaccharide (LPS), the main outer membrane component of endotoxin of Gram-negative bacteria, is the most common reagent to duplicate ALI/ARDS model which is similar to ALI/ARDS patients induced by severe infection in clinic. Inflammation and related effector cells, such as neutrophil and macrophage is actived by stimulating with LPS. Uncontrolled release of multiple inflammatory mediators and cytokines including TNF-α, IL-1β, IL-6, PAF have been considered to contribute to the injury of microvascular endothelium and alveolar epithelium. As a result, vascular permeability increases which results in the formation of pulmonary edema, hyaline membrane and interstitial fibrosis. Therefore inflammation and related effector cells, inflammatory
引文
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