摘 要: 目的 观察双氢青蒿素(dihydroartemisinin,DHA)对矽肺大鼠肺组织中转化生长因子-b1(TGF-b1)、Smad2/3、Ⅰ型胶原蛋白(Col-Ⅰ)表达的影响。方法 60只雄性SD大鼠随机分成对照组、模型组、DHA组,每组20只。模型组和DHA组给予1ml二氧化硅(SiO2)混悬液造模,对照组给予1ml生理盐水造模,造模后第2天开始灌胃给药,DHA组每只大鼠给予DHA75mg/kg灌胃,模型组和对照组给予1ml/100g生理盐水灌胃,每周给药6d,连续给药4周,并于第7、14、28天处死大鼠取肺组织,检测肺脏器系数,观察肺组织病理学变化,免疫印迹(Western blot)法检测TGF-b1、Smad2/3、Col-Ⅰ的蛋白表达。结果 与对照组相比,DHA组肺系数升高,差异具有统计学意义(P<0. 01);与模型组相比,DHA组肺系数降低,差异有统计学意义(P<0. 05);苏木素-伊红(HE)染色法显示DHA 组肺泡内的巨噬细胞和中性粒细胞低于模型组。 Western blot实验结果显示,与模型组相比,DHA组TGF-b1、Smad2/3、Col-Ⅰ蛋白表达降低,差异具有统计学意义(P<0. 05)。结论 DHA可以降低矽尘大鼠肺系数,减轻大鼠肺组织炎症,减少肺泡内巨噬细胞和中性粒细胞浸润,抑制TGF-b1、Smad2/3、Col-Ⅰ蛋白的表达,起到抑制肺纤维化作用,其机制可能与调控TGF-b1/Smad信号通路有关。 |
关键词: 双氢青蒿素(DHA) 大鼠 二氧化硅(SiO2) 肺纤维化 |
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基金项目: 山东省医学科学院医药卫生科技创新工程 |
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Effect of dihydroartemisinin on expression of TGF-β1,Smad2/3 and Col-Ⅰproteins in lung tissues of silicosis rats |
ZHENG Yi-jiao, LI Xia, GAO Shan-shan, SUN Lin
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School of Medicine and Life Science, Universicy of Jinan, Shandong Academy of Medicine Sciences, Jinan 250062, China)
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Abstract: Objective To observe the effects of dihydroartemisinin (DHA) on the expressions of TGF-b1, Smad2 / 3 and Ⅰtype collagen (Col-Ⅰ) in lung tissues of silicosis rats. Methods A total of 60 male Sprague-Dawley rats were randomly divided into 3 groups: control group, silicosis model group, and dihydroartemisinin group, each group had 20 rats. Rats in model group and dihydroartemisnin group were given 1 ml of silicon dioxide suspension, the control rats were given 1 ml of physiological saline. On the second day, the administered rats were intragastrically given with dihydroartemisinin ( 75 mg / kg), the rats of model and control groups were only given of 1 ml / 100 g of saline, the drug administration lasted for 4 weeks, 6 days per week.The rats of each group were killed on the 7th, 14th, and 28th day, respectively, to determine the lung coefficient, lung histopathological change, and the protein expression of TGF-b1、 Smad2 / 3 and Col-Ⅰ by Western blot technique. Results The results showed that compared with control group, the lung coefficients of rats in dihydroartemisinin group was significantly increased(P <0. 01), but still lower than that of model group (P <0. 05). HE staining showed that the alveolar infiltration of macrophages and neutrophils in rats of dihydroartemisinin-treated group were reduced than that in rats of model group. Western blot detection also showed that the expression of TGF-b1, Smad2 / 3 and Col-Ⅰ protein in lung tissues of dihydroartemisinin administrated rats were decreased as well compared with that of model rats (P <0. 05). Conclusion The results suggested that dihydroartemisinin could reduce the lung coefficient and pulmonary inflammation of silica exposed rats, alleviate the alveolar infiltration of macrophages and neutrophils, inhibite the expression of TGF-b1, Smad2 / 3 and Col-Ⅰ protein, thereby inhibite pulmonary fibrosis; the mechnism might be related to its regulating effect in TGF-b1 / Smad signaling pathway. |
Keywords: dihydroartemisinin (DHA) rats silicon dioxide (SiO2 ) pulmonary fibrosis |