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目的观察缬沙坦对哮喘小鼠气道炎症和早期重构的影响。方法 40只小鼠随机分为4组,正常对照组、模型组、地塞米松(2 mg.kg-1)组和缬沙坦(50 mg.kg-1)组,每组10只。卵清蛋白致敏建立哮喘模型,给药组每次雾化前1 h分别予相应药物灌胃,正常对照组和模型组给予等量生理盐水。观察肺组织病理学改变,记录支气管周围嗜酸粒细胞(Eos)计数、杯状细胞百分比、黏液分泌和炎症细胞评分,测定平滑肌面积。采用RT-PCR检测转化生长因子β1(TGF-β1)mRNA,Western blot免疫印迹和免疫组织化学方法检测其蛋白表达水平。结果模型组支气管周围Eos计数、杯状细胞百分比、炎症细胞评分、黏液分泌评分、平滑肌面积、TGF-β1mRNA和蛋白表达水平均明显高于正常对照组(P<0.01),地塞米松组和缬沙坦组上述指标均明显低于模型组(P<0.01)。缬沙坦组Eos计数、杯状细胞百分比、炎症细胞和黏液分泌评分高于地塞米松组(P<0.05),气道平滑肌面积、TGF-β1mRNA和蛋白表达水平2组间无显著差异(P>0.05)。TGF-β1蛋白表达水平与平滑肌面积正相关(r=0.467,P<0.01)。结论缬沙坦具有抑制哮喘气道炎症和早期重构的作用,其机制可能与抑制气道内TGF-β1表达有关。
Objective To observe the effects of valsartan on airway inflammation and early remodeling in asthmatic mice. Methods Forty mice were randomly divided into 4 groups: normal control group, model group, dexamethasone group (2 mg.kg-1) and valsartan (50 mg.kg-1) group. Ovalbumin sensitized asthmatic model was established. Each group in the administration group was given gavage 1 h before each atomization, and the normal control group and model group were given the same amount of normal saline. The histopathological changes of the lungs were observed. Peripheral bronchial eosinophils (Eos) count, goblet cell percentage, mucus secretion and inflammatory cell score were recorded to measure the smooth muscle area. Transforming growth factor β1 (TGF-β1) mRNA was detected by RT-PCR. The protein expression was detected by Western blot and immunohistochemistry. Results Eos count, goblet cell percentage, inflammatory cell score, mucus secretion score, smooth muscle area, TGF-β1 mRNA and protein expression in the bronchus of the model group were significantly higher than those in the normal control group (P <0.01) The above indexes in sartan group were significantly lower than those in model group (P <0.01). The scores of Eos, goblet cells, inflammatory cells and mucus secretion in valsartan group were higher than those in dexamethasone group (P <0.05), but there was no significant difference between the two groups in airway smooth muscle area, TGF-β1 mRNA and protein expression > 0.05). The level of TGF-β1 protein was positively correlated with smooth muscle area (r = 0.467, P <0.01). Conclusion Valsartan can inhibit airway inflammation and early remodeling of asthma. The mechanism may be related to the inhibition of TGF-β1 expression in the airway.