脓毒症诱导的急性呼吸窘迫综合征与肾素-血管紧张素系统

目的 研究脓毒症诱导的急性呼吸窘迫综合征(ARDS)与肾素-血管紧张索系统(RAS)的关系及其机制.方法 雄性BALB/c小鼠60只随机分3组(n=20):正常对照组,假手术组,手术组.应用盲肠结扎穿孔术(CLP)诱导ARDS动物模型,采用术后18 h小鼠动脉血气分析、肺湿干质量比(W/D)和肺组织病理等作为肺损伤指标;并在术后6 h检测血管紧张素转化酶(ACE)、ACE2及血管紧张素Ⅱ(AngⅡ)的变化.结果 术后18 h手术组较假手术组小鼠肺水明显增多(W/D:6.08±0.64比4.38±0.93,P<0.01),缺氧加重PaO2:(40.80±5.03)mm Hg比(72.80±4.32)mm Hg,P<0.01],氧合指数明显下降(PaO2/FiO2:194.30±23.90比346.70±20.50,P<0.01),且肺病理显示手术组小鼠肺出现明显的炎性细胞渗出、肺水肿和间隔增厚等改变.术后6 h手术组小鼠肺组织和血中AngⅡ表达量较假手术组明显升高(P<0.01).免疫组织化学显示假手术组和手术组小鼠肺组织中血管壁可见明显的ACE表达,手术组肺组织ACE2表达较其他2组弱.结论 脓毒症诱导的ARDS存在RAS系统激活,其中Ang Ⅱ表达增加可能加重肺损伤,而ACE2减少可能是AngⅡ增高的原因.

Sepsis-induced acute respiratory distress syndrome and renin-angiotensin system

Objective To study the mechanism of sepsis- induced acute respiratory distress syndrome (ARDS) and its correlation with renin-angiotensin system. Methods Male BALB/c mice were randomly divided into 3 groups (n=20)-the normal group, sham group, and cecal ligation and puncture (CLP) group. Sepsis-induced ARDS models were established by CLP. Blood gas, wet/dry lung weight ratio (W/D) , lung tissue histology as lung injury markers were examined 18 h post-CLP. Moreover, levels of several key enzymes from RAS angiotensin converting enzyme (ACE), ACE2 and angiotensin Ⅱ (Ang Ⅱ)] were detected 6 h post-CLP. Results CLP group mice showed a significant increase in lung water (W/D: 6.08±0.64 vs 4.38±0.93, P<0.01), hypoxia aggravation PaO2: (40.80±5.03) mm Hg vs (72.80±4.32) mm Hg, P<0.01] and decrease in oxygenation index (PaO2/FiO2: 194.30±23.90 vs 346.70±20.50, P<0.01) 18 h post-CLP compared to sham group. In addition, lung histology revealed inflammatory infiltration, alveolar edema and alveolar-capillary membrane thickening in CLP mice. Six hours after CLP, Ang Ⅱ protein was markedly increased in mice lung and plasma of CLP group than that of sham group, P<0.01. Immunohistochemistry showed an obvious expression of ACE in mice lung vessel wall in sham and CLP group associated with a decrease of lung ACE2 in CLP group than that of the other two groups. Conclusions RAS is activated in sepsis-induced ARDS. The increase of Ang Ⅱ expression can promote lung injury, and the increase of Ang Ⅱ may be correlated with the decrease of ACE2.