依那西普对博来霉素致大鼠肺间质性病变的影响

Effects of etanercept on rats with bleomycin induced interstitial lung disease

目的观察依那西普对博来霉素诱导的大鼠肺间质性病变的影响，并探讨其可能的作用机制。方法将36只雄性SD大鼠按随机数字表法分为对照组、模型组和治疗组（依那西普），每组12只。采用博来霉素诱导大鼠肺纤维化模型，治疗组予依那西普干预。观察比较造模后第14、21天各组大鼠肺组织病理及羟脯氨酸的变化，免疫组织化学染色方法检测转化生长因子β1（TGF-β1）、Smad2／3的表达。结果模型组及治疗组病理检查可见明显肺泡炎症改变、胶原沉积和纤维化形成，且治疗组各时期肺泡炎症和肺纤维化程度均较模型组减轻（P〈0．05）。治疗组各时期羟脯氨酸的表达较模型组均减少（P〈0．05）。免疫组织化学染色结果显示，与对照组相比，模型组和治疗组大鼠肺组织中的TGF-β1、Smad2／3表达均明显增加（P〈0．05），但治疗组表达较模型组减少（P〈0．05）。结论依那西普可改善博来霉素致大鼠肺间质性病变的程度，其作用机制可能与下调TGF-β1和Smad2／3水平有关。

Objective To explore the effects of etanercept on bleomycin - induced interstitial lung disease in rats and discuss the mechanism invovled. Methods A total of 36 male SD rats were randomly divided into three groups： a control group, a model group and a treatment group （n = 12）. A rat model of interstitial lung disease was established through bleomycin induction. Meanwhile, etanercept were used in the treatment group. On Days 14 and 21, the patholog- ical changes of each group were observed, while the levels of hydroxyproline （HYP）, TGF-β1 and Smad2/3 were de- tected in lung tissues. Results Alveolar inflammatory changes, collagen deposition and fibrosis changes could be clearly observed in the model and treatment groups, while the treatment group showed relieved alveolitis and fibrosis compared with the model group at each time point （ P 〈0. 05 ）. Compared with the model group, the level of HYP was reduced in the treatment group at each time point （P 〈0. 05 ）. According to immunochemical analysis, enhanced expression of TGF-β1 and Smad2/3 were found in the model and treatment groups （ P 〈 0.05 ）, where the treatment group produced re- markable less amounts of TGF-β1 and Smad2/3 than the model group （ P 〈 0.05 ）. Conclusions Etanercept can im- proved the pathological changes of bleomycin - induced interstitial lung disease in rats, which may be associated with its down - regulation of TGF-β1 and Smad2/3.