血管生成素-1对脓毒症小鼠肺血管通透性的影响

Effect of angiopoietin - 1 on pulmonary vascular permeability in septic mice

目的探讨外源性血管生成素-1（Ang-1）对脓毒症小鼠肺血管通透性的影响。方法腹腔注射脂多糖（LPS）制作脓毒症小鼠模型。64只BALB／c小鼠随机分为Ns组、Ang-1组、LPS组和LPS＋Ang-1组（n=16）。各组经处理12h后，分别收集血浆、肺泡灌洗液及肺组织标本。ELISA法测定血浆Ang-1、Ang-2浓度并计算Ang-2／Ang-1比值，测定血浆、肺泡灌洗液的总蛋白浓度并计算肺通透指数（LPI），测定肺组织湿干比及观察肺组织病理变化。结果Ang-1组血浆Ang-1浓度较Ns组明显升高（P〈0．05）。LPS组和LPS＋Ang-1组血浆Ang-1浓度较Ns组均明显降低（P〈0．01），而血浆Ang-2浓度及Ang-2／Ang-1比值较Ns组均明显升高（P〈0．01）。LPS＋Ang-1组血浆Ang-1浓度较LPS组明显升高（P〈0．01）。且血浆Ang-2浓度及Ang-2／Ang-1比值较LPS组明显降低（P〈0．01）。Ang-2／Ang-1比值与小鼠肺湿干比呈明显正相关（r=0．76，P〈0．01）。LPS组肺湿干比、肺通透指数较NS组明显升高（P〈0．01），LPS＋Ang-1组肺湿干比、肺通透指数较LPS组明显降低（P〈0．01），且肺组织病理渗出水肿较LPS组明显好转。结论外源性Ang-1通过调节脓毒症小鼠Ang-2／Ang-1失平衡而发挥降低肺血管通透性及改善肺水肿作用。

Objective To investigate the effect of exogenous angiopoietin - 1 （ Ang - 1 ） on pulmonary vascular permeability in septic mice. Methods Mice were made into sepsis model by the injection of lipopolysaccharide （LPS） intraperitoneally （ip）. 64 BALB/c mice were randomly divided into NS group, Ang - 1 group, LPS group and LPS ＋ Ang - 1 group （n = 16）. After 12 hours, plasma, broncho - alveolar lavage fluid （BALF） and lung tissue samples were collected. The plasma levels of Ang - 1, angiopoietin -2 （Ang -2） were tested by ELISA and Ang -2/Ang - 1 ratio was calculated. The total protein concentration of plasma and the BALF were tested and the lung permeability index （LPI） was calculated. The ratio of wet weight to dry weight （W/D） of lung was calculated, and lung tissue pathological changes were observed. Results The plasma Ang - 1 level was higher in Ang - 1 group than in the NS group（P 〈 0.05 ）. Compared with NS group, the plasma Ang- 1 level was lower （ P 〈0. 01 ）, but their plasma levels of Ang - 2 and Ang - 2/Ang - 1 ratio was higher （ P 〈 0.01 ） in LPSgroup and LPS ＋ Ang- 1 group. The plasma Ang- 1 level in LPS ＋ Ang- 1 group was significantly higher compared with LPS group （P 〈 0.01 ）, and the plasma level of Ang -2 and Ang -2/ Ang- 1 ratio was significantly lower compared with the LPS group（P 〈 0.01 ）. Ang -2/Ang - 1 ratio and wet to dry ratio of mice lung was significantly positively correlated（r =0.76, P 〈 0.01 ）. The ratio of wet to dry of the lung, lung permeability index in LPS group were significantly higher compared with NS group （ P 〈 0.01 ）. The lung＇s the ratio of wet to dry and lung permeability index in LPS ＋ Ang - 1 group was significantly lower compared with the LPS group（ P 〈 0.01 ）, and pulmonary edema in LPS ＋ Ang - 1 group was significantly improved compared with LPS group. Conclusion Exogenous Ang - 1 can decrease pulmonary vascular permeability and reduce pulmonary edema in septic mice by regulating Ang - 2/Ang - 1 balance.