姜黄素对急性肺损伤大鼠肺组织转化生长因子-β_1/Smads信号通路的影响

Impact of curcumin on transforming growth factor-β_1 and Smads signaling pathway of acute lung injury in rats

目的探讨姜黄素在大鼠急性肺损伤中早期应用对转化生长因子-β1(TGF-β1)/Smads信号通路的影响。方法健康雄性Sprague Dawley大鼠36只,随机分为空白对照组、模型组和姜黄素组,每组12只。采用博来霉素气管内一次性滴注给药建立模型,造模第2天开始姜黄素组大鼠给予100 mg·kg-1·d-1姜黄素灌胃,模型组和空白对照组大鼠以等体积生理盐水灌胃,用药第3、7天分批将大鼠处死,采集肺组织标本,采用免疫组织化学法观察肺组织TGF-β1以及胞内信号转导蛋白Smads(Smad2/3、7)的表达变化。结果空白对照组大鼠第3、7天时肺组织结构未见异常。模型组大鼠第3天肺组织以肺泡急性炎症为主,毛细血管充血扩张,肺泡腔内可见大量炎性渗出;第7天部分肺泡间隔增厚,管壁增厚,肺泡间隔及肺泡腔内炎性细胞浸润增多,较第3天严重。姜黄素组大鼠第3、7天肺组织部分细支气管及肺泡腔内可见少量散在分布炎性细胞,与同期模型组比较炎症和损伤程度均有所减轻。模型组大鼠肺组织中TGF-β1、Smad2/3蛋白的表达水平与空白对照组比较均显著升高(P<0.01),姜黄素组大鼠肺组织TGF-β1、Smad2/3表达较模型组显著降低(P<0.01)。模型组和姜黄素组大鼠肺组织Smad7表达水平与空白对照组比较均显著降低(P<0.01,P<0.05),且姜黄素组显著高于模型组(P<0.01)。结论姜黄素对大鼠急性肺损伤的早期干预和治疗可能是通过下调Smad2/3蛋白和上调Smad7蛋白,进而影响TGF-β1/Smads信号通路。

Objective To investigate the effect of curcumin on transforming growth factor-β1 （TGF--β1）/Smads signal pathway in rats with acute lung injury. Methods Thirty-six healthy male Sprague Dawley rats were randomly divided into blank control group,model group and curcumin group, with 12 cases in each group. The model was established by bleomycin endotracheal one-time drip, and curcumin group was given 100 mg·kg-1 . d-1 by intragastric administration ,while the blank control group and model group was given saline lavage with the same volume. After the drug treatment for 3 and 7 days ,the rats were sacrificed and the lung tissues was collected. The TGF-β1 and intracellular signal transduction protein Smads（ Smad2/3, 7） expression changes in lung tissue were observed by using immunohistochemistry. Results The lung structure of rats in blank control group at the 3~d ,7th day was not abnormal. The lung tissue of rats in model group showed acute pulmonary alveoli inflammation, capillaries dilatation and congestion and alveolar visible large amount of inflammatory exudates at the 3rd day, and part of the alveolar septum thickening, vessel wall thickening, alveolar septa and alveolar inflammatory cell infiltration increas- ing at the 7th day,which was more serious than the 3rd day. The lung structure of rats in curcumin group at the 3rd and 7th day of lung tissue showed some diffused distribution inflammatory cells in bronchiole and alveolar cavity, which was mitigated, in in- flammation and injury compared with the model group at the same time. The TGF-β1 and Smad2/3 expression in mode group were higher significantly than those in the blank control group（P 〈 0.01 ）. The TGF-β1 and Smad2/3 expression in curcumin group decreased significantly compared with those in model group（P 〈 0.01 ）. The Smad7 expression in model group and curcumin group was lower significantly than that in the blank control group（ P 〈 0.01 ,P 〈 0.05 ） ,which increased significantly in curcumin group compared with model group（P 〈 0.01 ）. Conclusion Curcumin early application has intervention and treat-ment effect on acute lung injury in rats, which may be through cutting Smad7 protein and raising Smad2/3 protein in order to affecting the TGF-β1/Smads signal pathways.