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目的探讨血管内皮生长因子(VEGF)、IFN-γ、IL-4在急性哮喘大鼠模型中的表达变化及其相关性及布地奈德混悬液干预后的变化。方法清洁级雄性SD大鼠36只随机分为对照组、哮喘组和布地奈德干预组。实验第1天和第8天,哮喘组和布地奈德干预组大鼠腹腔注射鸡卵清蛋白(OVA)/氢氧化铝混合液致敏2次,第15天开始给予大鼠喷雾(10 g/L OVA,30 min/d),连续激发2周,制备哮喘模型。对照组致敏和激发均以9 g/L盐水替代OVA。布地奈德干预组于每次抗原激发前0.5 h予布地奈德雾化吸入,12 h后相同剂量再雾化1次,共2周。各组大鼠末次激发24 h后处死,收集血液与支气管肺泡灌洗液(BALF)。应用ELISA法测定其血清和BALF中IL-4、IFN-γ和VEGF水平。结果哮喘组和布地奈德干预组大鼠BALF和血清IL-4水平均显著高于对照组(P<0.01,0.05);布地奈德干预组BALF和血清IL-4水平均显著低于哮喘组(Pa<0.01)。哮喘组BALF和血清IFN-γ水平均显著低于对照组和布地奈德干预组(Pa<0.01)。哮喘组BALF和血清VEGF水平均显著高于对照组和布地奈德干预组(Pa<0.01);布地奈德干预组血清和BALF中VEGF水平与对照组比较均无显著差异。BALF中IL-4与VEGF水平呈显著正相关(r=0.818 P<0.01),IFN-γ水平与VEGF水平呈显著负相关(r=-0.646 P<0.01);血清IL-4水平与VEGF水平呈显著正相关(r=0.690 P<0.01),IFN-γ水平与VEGF水平呈显著负相关(r=-0.479 P<0.01)。结论哮喘急性发作时存在Th1/Th2失衡,且Th1/Th2失衡与VEGF的表达存在明显的相关性,布地奈德雾化吸入可调节Th1/Th2的平衡及抑制VEGF的表达。
Objective To investigate the expression changes of vascular endothelial growth factor (VEGF), IFN-γ and IL-4 in acute asthmatic rat model and the correlation between the changes and the intervention of budesonide suspension. Methods Thirty-six male Sprague-Dawley rats were randomly divided into control group, asthma group and budesonide intervention group. On day 1 and day 8 of the experiment, the rats in the asthma group and the budesonide intervention group were sensitized twice with OVA / aluminum hydroxide mixture and the rats were sprayed on the 15th day (10 g / L OVA, 30 min / d), continuous stimulation for 2 weeks to prepare asthma model. The control group was sensitized and challenged with OVA at 9 g / L saline. The budesonide intervention group inhaled budesonide 0.5 h prior to each antigen challenge, and the same dose was resprayed 12 times for 2 weeks. Rats in each group were sacrificed 24 h after the last challenge, and blood and bronchoalveolar lavage fluid (BALF) were collected. The levels of IL-4, IFN-γ and VEGF in serum and BALF were measured by ELISA. Results The levels of IL-4 in BALF and serum in asthma group and budesonide-treated group were significantly higher than those in control group (P <0.01, 0.05). The levels of BALF and serum IL-4 in budesonide intervention group were significantly lower than those in asthma group (Pa <0.01). The levels of BALF and serum IFN-γ in asthma group were significantly lower than those in the control group and budesonide intervention group (P <0.01). The levels of BALF and serum VEGF in asthma group were significantly higher than those in the control group and budesonide intervention group (P <0.01). There was no significant difference in the level of VEGF between the budesonide intervention group and the control group. There was a significant positive correlation between IL-4 and VEGF levels in BALF (r = 0.818 P <0.01), IFN-γ and VEGF levels (r = -0.646 P <0.01) (R = 0.690 P <0.01). There was a significant negative correlation between the level of IFN-γ and VEGF (r = -0.479 P <0.01). Conclusions Th1 / Th2 imbalance exists in acute asthma attack, and the imbalance of Th1 / Th2 has a significant correlation with the expression of VEGF. Budesonide inhalation can regulate the balance of Th1 / Th2 and inhibit the expression of VEGF.