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目的:探讨重组人血管内皮抑制素、孟鲁司特和布地奈德对小鼠哮喘模型气道重塑的影响。方法:BALB/c小鼠按随机数字表法分为正常对照组、哮喘模型组(100μg 0VA腹腔内注射)、重组人血管内皮抑制素组(2.25 mg·kg_1腹腔注射)、孟鲁司特组(3mg·kg_1灌胃)、布地奈德雾化液吸入组(1mg·kg_1雾化吸入),每组各10只。用酶联免疫吸附测定(ELISA)法对各组小鼠支气管肺泡灌洗液(BALF)中血管内皮生长因子(VEGF)进行定量分析;采用医学图像分析软件测定小支气管管壁面积(S1)、管腔的内周长(P1)、管壁平滑肌面积(S2)、小血管平滑肌面积(S3)及内周长(P2)。结果:对照组支气管管壁面积(S1/P1)、支气管平滑肌面积(S2/P1)、血管壁平滑肌面积(S3/P2)分别为(16.4±1.5),(2.2±0.4)和(5.2±0.6)μm~2·μm_1,模型组S1/P1,S2/P1,S3/P2分别为(35.3±4.4),(12.9±2.4)和(23.6±4.8)μm~2·μm_1,两组比较差异均有统计学意义(P<0.001)。给药各组S1/P1,S2/Pl和S3/P2分别为:重组人血管内皮抑制素组(24.5±0.7),(5.5±0.5)和(9.3±1.2)μm~2·μm_1;孟鲁司特组(22.8±4.3),(5.3±1.8)和(15.0±2.1)μm~2·μm_1;布地奈德组(21.4±2.5),(4.9±1.1)和(13.8±1.4)μm~2·μm_1,给药各组与模型组比较差异均有统计学意义(P<0.05)。给药各组间比较不存在显著性差异。各组BALF中的VEGF水平:对照组(19.2±3.8)pg·mL_1,模型组(108.48±28.4)pg·mL_1,重组人血管内皮抑制素组(70.3±20.1)pg·mL_1,孟鲁司特组(89.3±23.4)pg·mL_1,布地奈德组(82.3±21.4)pg·mL_1,与模型组相比,给药组BALF中的VEGF水平显著下降(P<0.05),具有统计学意义。结论:血管内皮生长因子在小鼠哮喘模型气道及肺内过度表达,重组人血管内皮抑制素、孟鲁斯特钠、布地奈德可显著减少VEGF在小鼠气道及肺内的表达。重组人血管内皮抑制素、孟鲁斯特钠、布地奈德均可以延缓气道重建包括减少气道壁增厚、气道平滑肌的增厚及气道内血管平滑肌的增厚。其中重组人血管内皮抑制素对气道内血管平滑肌的增厚的改善作用更加明显。
Objective: To investigate the effect of recombinant human endostatin, montelukast and budesonide on airway remodeling in mouse asthma model. Methods: BALB / c mice were randomly divided into normal control group, asthma model group (100μg 0VA intraperitoneal injection), recombinant human endostatin group (2.25 mg · kg_1 ip), montelukast group (3 mg · kg -1) and budesonide inhalation group (1 mg · kg -1 inhalation), 10 rats in each group. The levels of vascular endothelial growth factor (VEGF) in bronchoalveolar lavage fluid (BALF) of mice in each group were quantitatively analyzed by enzyme linked immunosorbent assay (ELISA); the area of bronchial wall (S1) The inner diameter of lumen (P1), smooth muscle area (S2), small vascular smooth muscle area (S3) and inner perimeter (P2). RESULTS: The mean bronchial wall area (S1 / P1), bronchial smooth muscle area (S2 / P1), and vascular wall smooth muscle area (S3 / P2) were (16.4 ± 1.5), (2.2 ± 0.4) and (5.2 ± 0.6 ) μm ~ 2 · μm_1. The difference of S1 / P1, S2 / P1 and S3 / P2 in the model group was (35.3 ± 4.4), (12.9 ± 2.4) and (23.6 ± 4.8) μm ~ There was statistical significance (P <0.001). The ratio of S1 / P1, S2 / P1 and S3 / P2 in the treated groups were (24.5 ± 0.7), (5.5 ± 0.5) and (9.3 ± 1.2) μm ~ (22.8 ± 4.3), (5.3 ± 1.8) and (15.0 ± 2.1) μm ~ 2 · μm_1 in budesonide group and 21.4 ± 2.5, 4.9 ± 1.1 and 13.8 ± 1.4 μm in budesonide group · Μm_1. There was significant difference between the administration groups and the model group (P <0.05). There was no significant difference between the two groups. The levels of VEGF in BALF in each group were 19.2 ± 3.8 pg · mL_1 in the control group, 108.48 ± 28.4 pg · mL_1 in the model group, 70.3 ± 20.1 pg · mL_1 in the recombinant human endostatin group, (89.3 ± 23.4) pg · mL_1, budesonide group (82.3 ± 21.4) pg · mL_1. Compared with the model group, the level of VEGF in BALF of the treated group was significantly decreased (P <0.05), which was statistically significant. Conclusion: Vascular endothelial growth factor is overexpressed in airway and lung of mouse asthma model. Recombinant human endostatin, montelukast sodium and budesonide can significantly reduce the expression of VEGF in airway and lung of mice. Recombinant human endostatin, montelukast sodium, budesonide can delay airway remodeling including reducing airway wall thickening, airway smooth muscle thickening and airway smooth muscle thickening. Among them, recombinant human endostatin can improve the thickening of airway smooth muscle more obviously.