【摘要】 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。更多还原

【Abstract】 Objective To evaluate theexpressionlevel of hypoxia-induciblefactor-1α(HIF-1α) intherat model of diet-induced obesity and asthma. Methods Forty male specific pathogen-free SD rats were randomly divided into four groups: normal body mass control group(group A),asthmatic rats with normal body mass(group B),obese control group(group C) and obese asthmatic rats(group D). The rats in both group A and B were fed basic diet,while those in group C and D were fed high-fat diet in order to establish diet-induced obese rat model. Rats in group B and D were sensitized and challenged with chicken ovalbumin(OVA) to establish the asthmatic model. The white cell count in bronchoalveolar lavage fluid(BALF) was performed. The total area of the airway wall(Wat) was measured by ImagePro Plus software and was standardized by the basement membrane perimeter(Pbm). The expression of HIF-1α in lung tissue was detected by immunohistochemistry. The concentration of HIF-1α in serum was determined by ELISA. The relationships of the total white cells in BALF and airway wall thickness( WAt /Pbm) with the expression of HIF-1α were analyzed by Pearson correlation analysis. Results The total number of white cells in BALF in group D was(98. 0 ± 5. 5) × 104/mL,which was significantly higher than those in group A(24.7 ±3.3) ×104/mL,group C(26. 1 ± 3. 8) × 104/mL and group B(87. 8 ± 7. 1) × 104/mL. The thickness of airway wall(WAt/Pbm) in group D was(9.91 ±0.56)m2/m,which was significantly higher than those in group A(6. 11 ± 0. 99) m2/m and group C(5. 99 ± 0. 83)m2/m,but when compared with that in group B(8. 60 ± 0. 53) m2/m,there was no significant difference. The percentage of HIF-1α positive cells in group D was(19.44 ±0.96)%,which was significantly higher than those in group A(2. 19 ± 0. 91)%,group C(2. 56 ± 0. 89)% and group B(18. 25 ± 1. 29)%(all P < 0. 05). The expression of HIF-1αin blood serum and BALF in group D were respectively(29. 107 ± 1. 576) ng /mL and(0. 511 ± 0. 011) ng /mL,which were significantly higher than those in group A [(19. 380 ± 1. 506) ng /mL and(0. 280 ± 0. 008) ng /mL,respectively],group C[(20.782 ±2.034) ng/mL and(0.281 ±0.010) ng/mL,respectively]and group B [(23.961 ±1.565) ng/mL and(0.397 ±0. 011) ng /mL,respectively]. The expression of HIF-1α was positively correlated with the total number of white cells in BALF and the airway wall thickness. Conclusion The expression of HIF-1α in serum and lung tissue from obese asthmatic rats significantly increases,which is positively correlated with the total number of white cells in BALF and the airway wall thickness.更多还原