血管生成素Ⅰ和血管生成素Ⅱ对哮喘患者气道血管通透性的作用
2007/06/27
血管内皮生长因子（Vascular endothelial growth factor，VEGF）可增强微血管的通透性。目前，血管生成素Ⅰ和血管生成素Ⅱ作为VEGF的调节因子正受到关注。为了明确他们在哮喘气道微血管通透性方面的作用， Hiroshi Kanazawa等做了以下的研究：在30名哮喘患者和12名正常人中进行了血管生成因子和气道血管通透性指数的测定，二周的筛选期后，所有哮喘患者被随机分组接受丙酸氟替卡松(400 μg/d)或孟鲁斯特(10 mg/d)为期十二周的治疗。结果发现在哮喘患者中诱导痰中VEGF和血管生成素Ⅰ和血管生成素Ⅱ的水平均较正常人显著增高，而且血管生成素Ⅰ水平和血管通透性指数成反比，但血管生成素Ⅱ水平和血管通透性指数成正相关。VEGF和血管生成素1水平在氟替卡松治疗后显著下降，而孟鲁斯特治疗组治疗后VEGF和血管生成素Ⅱ水平显著下降。虽然在两组治疗组中VEGF的水平有所不同，但血管通透性指数在孟鲁斯特治疗组和氟替卡松治疗组的水平一致。而且，氟替卡松治疗组血管通透性指数的改善与血管生成素Ⅰ水平的下降成反比，而孟鲁斯特治疗组的治疗与血管生成素Ⅱ水平的下降成正相关。
所以，从这项研究中发现：血管生成素Ⅰ和血管生成素Ⅱ在调节哮喘患者受VEGF刺激后的微血管通透性方面呈互补的协同作用。而联合白三烯受体拮抗剂和糖皮质激素可以有效地改善微血管血浆渗漏，从而在治疗支气管哮喘中发挥更大作用。
（汤葳 上海交通大学附属瑞金医院呼吸科 200025 摘译 ）
( Chest. 2007;131:1035-1041)
Roles of Angiopoietin-1 and Angiopoietin-2 on Airway Microvascular Permeability in Asthmatic Patients*
Hiroshi Kanazawa, MD, PhD; Saeko Nomura, MD, PhD and Kazuhisa Asai, MD, PhD
* From the Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Correspondence to: Hiroshi Kanazawa, MD, PhD, Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, 1–4-3, Asahi-machi, Abenoku, Osaka, 545-8585, Japan; e-mail: kanazawa-h@med.osaka-cu.ac.jp
Abstract
Background: Vascular endothelial growth factor (VEGF) increases microvascular permeability. Recently, considerable attention has been devoted to the physiologic roles of angiopoietin-1 and angiopoietin-2 as regulatory factors of VEGF. This study was designed to examine the roles of angiopoietin-1 and angiopoietin-2 in controlling airway microvascular permeability in asthma.
Methods: Levels of these angiogenic factors and airway vascular permeability index were examined in 30 asthmatics and 12 control subjects. After 2-week run-in period, all asthmatics were randomly assigned to receive fluticasone propionate (400 μg/d) or montelukast (10 mg) for 12 weeks.
Results: VEGF, angiopoietin-1, and angiopoietin-2 levels in induced sputum were significantly higher in asthmatics than in control subjects. We found an inverse correlation between angiopoietin-1 level and vascular permeability index in asthmatics, while there was a positive correlation between angiopoietin-2 level and that index. VEGF and angiopoietin-1 levels were significantly decreased after fluticasone therapy, while VEGF and angiopoietin-2 levels were significantly decreased after montelukast therapy. Although VEGF levels after treatment were different between two groups, vascular permeability index in the montelukast group was the same level as that in the fluticasone group. Moreover, improvement in vascular permeability index after fluticasone therapy was inversely correlated with decrease in angiopoietin-1 level, while that after montelukast therapy was positively correlated with decrease in angiopoietin-2 level.
Conclusions: Angiopoietin-1 and angiopoietin-2 play complementary and coordinated roles in regulating microvascular permeability stimulated by VEGF in asthma. Combination of corticosteroids with leukotriene antagonists might effectively improve plasma leakage and provide a new strategy in treating bronchial asthma.
Key Words: airway remodeling·bronchial asthma·vascular endothelial growth factor
所以，从这项研究中发现：血管生成素Ⅰ和血管生成素Ⅱ在调节哮喘患者受VEGF刺激后的微血管通透性方面呈互补的协同作用。而联合白三烯受体拮抗剂和糖皮质激素可以有效地改善微血管血浆渗漏，从而在治疗支气管哮喘中发挥更大作用。
（汤葳 上海交通大学附属瑞金医院呼吸科 200025 摘译 ）
( Chest. 2007;131:1035-1041)
Roles of Angiopoietin-1 and Angiopoietin-2 on Airway Microvascular Permeability in Asthmatic Patients*
Hiroshi Kanazawa, MD, PhD; Saeko Nomura, MD, PhD and Kazuhisa Asai, MD, PhD
* From the Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Correspondence to: Hiroshi Kanazawa, MD, PhD, Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, 1–4-3, Asahi-machi, Abenoku, Osaka, 545-8585, Japan; e-mail: kanazawa-h@med.osaka-cu.ac.jp
Abstract
Background: Vascular endothelial growth factor (VEGF) increases microvascular permeability. Recently, considerable attention has been devoted to the physiologic roles of angiopoietin-1 and angiopoietin-2 as regulatory factors of VEGF. This study was designed to examine the roles of angiopoietin-1 and angiopoietin-2 in controlling airway microvascular permeability in asthma.
Methods: Levels of these angiogenic factors and airway vascular permeability index were examined in 30 asthmatics and 12 control subjects. After 2-week run-in period, all asthmatics were randomly assigned to receive fluticasone propionate (400 μg/d) or montelukast (10 mg) for 12 weeks.
Results: VEGF, angiopoietin-1, and angiopoietin-2 levels in induced sputum were significantly higher in asthmatics than in control subjects. We found an inverse correlation between angiopoietin-1 level and vascular permeability index in asthmatics, while there was a positive correlation between angiopoietin-2 level and that index. VEGF and angiopoietin-1 levels were significantly decreased after fluticasone therapy, while VEGF and angiopoietin-2 levels were significantly decreased after montelukast therapy. Although VEGF levels after treatment were different between two groups, vascular permeability index in the montelukast group was the same level as that in the fluticasone group. Moreover, improvement in vascular permeability index after fluticasone therapy was inversely correlated with decrease in angiopoietin-1 level, while that after montelukast therapy was positively correlated with decrease in angiopoietin-2 level.
Conclusions: Angiopoietin-1 and angiopoietin-2 play complementary and coordinated roles in regulating microvascular permeability stimulated by VEGF in asthma. Combination of corticosteroids with leukotriene antagonists might effectively improve plasma leakage and provide a new strategy in treating bronchial asthma.
Key Words: airway remodeling·bronchial asthma·vascular endothelial growth factor
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