血管生成素2在大鼠内毒性急性肺损伤中的作用与机制研究

目的：探讨血管生成素-2(Ang-2)在脂多糖(LPS)致大鼠急性肺损伤(ALI)时的表达及其机制。方法48只清洁级SD大鼠随机分为正常对照组、1 mg/kg LPS组、5 mg/kg LPS组和10 mg/kg LPS组,每组12只。 LPS组尾静脉注射不同剂量LPS复制ALI模型,对照组注射同等体积生理盐水,留取肺组织标本,观察肺湿/干重( W/D)比值、HE染色光镜观察肺组织标本病理改变并进行肺损伤评分,各组ELISA法检测血浆中Ang-2与血管内皮生长因子( VEGF)的表达,Westernblot方法检测肺组织中Ang-2的蛋白表达情况。结果 LPS注射进入大鼠尾静脉6 h后,光镜下可见肺组织内的炎性细胞浸润,肺泡隔增宽,肺间质水肿和肺结构破坏等病理改变；LPS各组的肺损伤评分与W/D比值明显高于对照组(P<0．05)；LPS不同剂量组血浆中Ang-2与VEGF的表达水平较对照组明显增高(P<0．05),血浆中Ang-2的表达与VEGF、肺损伤评分呈正相关(r=0．826,P<0．05；r=0．775,P<0．05)；LPS不同剂量组与Ang-2蛋白的表达水平呈现剂量效应关系(P<0．05)。结论 Ang-2参与大鼠ALI的发病过程,且Ang-2水平增高与ALI严重程度有关。

Effect of angiopoietin-2 on LPS-induced rat acute lung injury

Objective To explore the expression and the potential effect of angiopoietin-2 ( Ang-2 ) in rats with acute lung injury (ALI). Methods Forty-eight male Sprague-Dawley(SD) rats were randomly divided into four groups(n=12), which were normal control group, 1 mg/kg lipopolysaccharide (LPS) group, 5 mg/kg LPS group and 10 mg/kg LPS group. The ALI models were produced through ve-nous injection of different doses of LPS, and the control group was injected with the same dose of saline. Lung samples were observed, lung wet and dry weight ratio ( W/D) , lung histopathology, and pathological score were detected. Plasma Ang-2 and vascular endothelial growth factor( VEGF) were assessed by enzyme-linked immunosorbent assay( ELISA) . Protein was extracted from lung tissues for determination of Ang2 by Western blot analysis. Results After 6 h of LPS injected into the tail vein of the rats, the inflammatory cell infiltration, alveolar septum widened, the changes of pulmonary interstitial edema and pulmonary pathological damage were seen in lung tissues under the light mi-croscope. The pathological score and W/D in LPS group were significantly higher than those in control group (P<0. 05). The plasma levels of Ang-2 and VEGF were significantly increased compared with control group (P<0. 05), and the plasma levels of Ang-2 were significantly positive correlated with VEGF levels (r=0. 826,P<0. 05) and pathological score (r=0. 775,P<0. 05). The expression of Ang-2 protein in different doses of LPS group was dose-dependent (P<0. 05). Conclusion Ang-2 is involved in the pathogenesis of acute lung injury in rats, and the level of Ang-2 is positively correlated with the severity of acute lung injury.