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目的观察缺氧诱导因子-1α(HIF-1α)在肥胖哮喘大鼠中的表达并探讨其作用。方法将40只清洁级雄性SD大鼠随机分为正常体质量对照组(A组)、正常体质量哮喘组(B组)、肥胖对照组(C组)、肥胖哮喘组(D组)。正常体质量组大鼠给予基础饲料,肥胖组大鼠给予高能饲料以建立肥胖大鼠模型。鸡卵清蛋白(OVA)致敏、激发,建立哮喘模型。对肺泡灌洗液(BALF)中白细胞进行计数。ImagePro Plus软件测定气管壁总面积(WAt),并以基底膜周长(Pbm)标准化,结果以气管壁厚度(WAt/Pbm)表示。免疫组织化学染色检测肺组织中HIF-1α的表达。ELISA测定血清中HIF-1α的水平。采用Pearson相关分析法分析HIF-1α的表达水平与BALF中白细胞总数、气管壁厚度的相关性。结果 D组大鼠BALF中白细胞总数为(98.0±5.5)×104/mL,较A组(24.7±3.3)×104/mL、B组(87.8±7.1)×104/mL、C组(26.1±3.8)×104/mL升高(P<0.05);D组大鼠WAt/Pbm为(9.91±0.56)m2/m,较A组(6.11±0.99)m2/m、C组(5.99±0.83)m2/m升高,与B组(8.60±0.53)m2/m差异无显著性意义;D组大鼠肺组织中HIF-1α的阳性细胞表达率为(19.44±0.96)%,较A组(2.19±0.91)%、B组(18.25±1.29)%、C组(2.56±0.89)%升高;D组的大鼠血清及BALF中HIF-1α浓度分别为(29.107±1.576)ng/mL、(0.511±0.011)ng/mL,较A组(19.380±1.506)ng/mL、(0.280±0.008)ng/mL,B组(23.961±1.565)ng/mL、(0.397±0.011)ng/mL,C组(20.782±2.034)ng/mL、(0.281±0.010)ng/mL升高;HIF-1α表达水平与BALF中白细胞总数、WAt/Pbm呈正相关。结论HIF-1α在肥胖哮喘大鼠血清及肺组织中的表达明显增加,与BALF中白细胞总数、气管壁厚度呈正相关。
Objective To observe the expression of hypoxia inducible factor-1α (HIF-1α) in obese asthmatic rats and to explore its role. Methods Forty clean male Sprague Dawley rats were randomly divided into normal weight control group (A group), normal body mass asthma group (B group), obese control group (C group) and obese asthma group (D group). The rats in the normal body weight group were given basic diet, and the obese rats were given high energy diet to establish the obese rat model. Chicken ovalbumin (OVA) sensitized, challenged, the establishment of asthma model. Leukocytes in BALF were counted. The total area of the tracheal wall (WAt) was determined by ImagePro Plus software and normalized to the basement membrane perimeter (Pbm). The results were expressed as the tracheal wall thickness (WAt / Pbm). Immunohistochemical staining was used to detect the expression of HIF-1α in lung tissue. ELISA to measure the level of HIF-1α in serum. Pearson correlation analysis was used to analyze the correlation between the expression level of HIF-1αand the total number of leucocytes and the thickness of tracheal wall in BALF. Results The total number of leukocytes in BALF of group D was (98.0 ± 5.5) × 104 / mL, which was significantly higher than that of group A (24.7 ± 3.3) × 104 / mL, group B (87.8 ± 7.1) × 104 / mL and group C (9.91 ± 0.56) m2 / m in group D compared with 6.11 ± 0.99 m2 / m in group D and 5.99 ± 0.83 in group C (P < m2 / m, which was not significantly different from that of group B (8.60 ± 0.53) m2 / m. The positive expression rate of HIF-1α in lung tissue of group D was (19.44 ± 0.96)%, 2.19 ± 0.91%, 18.25 ± 1.29% in group B and 2.56 ± 0.89% in group C. The concentrations of HIF-1α in serum and BALF in group D were (29.107 ± 1.576) ng / mL, (0.511 ± 0.011) ng / mL, which was significantly higher than that in group A (19.380 ± 1.506) ng / mL, 0.280 ± 0.008 ng / mL, 23.961 ± 1.565 ng / mL, (20.782 ± 2.034) ng / mL, (0.281 ± 0.010) ng / mL in C group. The expression level of HIF-1α was positively correlated with the total number of leucocytes and WAt / Pbm in BALF. Conclusion The expression of HIF-1α in serum and lung tissues of obese asthmatic rats increased significantly, which was positively correlated with the total number of leucocytes and the thickness of tracheal wall in BALF.