机构地区:[1]枣庄市疾病预防控制中心健康教育科,山东枣庄277100 [2]济南大学山东省医学科学院医学与生命科学学院,山东济南250062 [3]山东省职业卫生与职业病防治研究院,山东第一医科大学(山东省医学科学院)毒理室,山东济南250062 [4]山东省职业卫生与职业病防治研究院,山东第一医科大学(山东省医学科学院)办公室,山东济南250062
出 处:《职业与健康》2020年第17期2329-2334,共6页Occupation and Health
基 金:山东省医学科学院医药卫生科技创新工程;山东省重点研发计划(2018GSF118102);山东省重点研发计划(2018GSF118212);山东第一医科大学学术提升计划(2019QL001)。
摘 要:目的研究抗肺纤中药颗粒的干预对染矽尘大鼠肺组织上皮-间质转化的影响及其可能的作用原因。方法将斯波累格·多雷(SD)大鼠随机分为4组,每组16只。对照组大鼠灌注1.0 mL 0.9%生理盐水造模,然后每天灌胃0.9%生理盐水;模型组、高剂量组和低剂量组大鼠均灌注1.0 mL 50 mg/mL SiO2悬浊液造模,其后模型组每天灌胃0.9%生理盐水,高剂量组和低剂量组大鼠分别灌胃1000、500 mg/kg中药,每天1次。于灌胃第14、28天处死大鼠,观察大鼠肺组织病理学变化,并检测大鼠肺组织转化生长因子-β1(TGF-β1)和转录激活因子(Smad2/3)的阳性表达及E-钙粘蛋白(E-cad)、波形蛋白(Vimentin)的蛋白表达水平。结果SiO2刺激14天和28天后,模型组大鼠肺组织有明显的炎症反应及胶原纤维的积聚,中药的干预可有效抑制其肺组织病理学的改变;中药干预后可升高大鼠肺组织E-cad的表达、降低肺组织Vimentin的表达水平,进而改善肺组织上皮-间质的转化,且高剂量组的效果较明显,差异均有统计学意义(均P<0.05);同时SiO2刺激14天和28天后,模型组大鼠肺组织TGF-β1的表达(15.78±3.09,17.73±3.09)及Smad2/3表达(4.91±1.12,5.86±1.55)明显升高,而中药的干预抑制了SiO2诱导的肺组织TGF-β1和Smad2/3蛋白的阳性表达,且高剂量组TGF-β1和Smad2/3的表达(12.87±2.52,1.98±0.57)较低,差异有统计学意义(P<0.05)。结论抗肺纤中药颗粒可改善大鼠肺泡炎症和矽肺纤维化的程度,抑制Si O2诱导的上皮-间质转化,该作用可能是大鼠肺组织中TGF-β1、Smad2/3蛋白阳性表达降低的结果。Objective To investigate the effects of anti-lung fibrosis traditional Chinese medicine particles intervention on epithelial-mesenchymal transition in lung tissues of rats exposed to silica and its possible pathways.Methods Sprague Dawley(SD)rats were randomly divided into 4 groups,16 rats in each group.Rats in the control group were perfused with 1.0 mL 0.9%normal saline to develop the model,and were administered with 0.9%normal saline daily.Rats in the model group,high-dose group and low-dose group were perfused with 1.0 mL 50 mg/mL SiO2 suspension to develop the model,and then rats in the model group were administered with 0.9%normal saline,rats in the high-dose group and the low-dose group were given 1000 mg/kg and 500 mg/kg Chinese medicine respectively,once a day.The rats were sacrificed on the 14 th and 28 th day of intragastric administration to observe the pathological changes of lung tissues and detect the positive expression of transforming growth factor-β1(TGF-β1)and activated transcription factor(Smad2/3)and the protein expression levels of E-cadherin(E-cad)and Vimentin in lung tissues.Results After 14 and 28 days of SiO2 stimulation,rats in model group had obvious inflammatory reaction and accumulation of collagen fibers,and the intervention of traditional Chinese medicine could effectively inhibit the pathological changes of lung tissues.After the intervention of traditional Chinese medicine,the expression of E-cad in lung tissues increased and the expression of Vimentin decreased,thereby improving epithelial-mesenchymal transition of lung tissues.The effect of highdose group was more obvious,and the difference was statistically significant(P<0.05).After 14 and 28 days of SiO2 stimulation,the expression of TGF-β1(15.78±3.09,17.73±3.09)and Smad2/3(4.91±1.12,5.86±1.55)in rat lung tissues in the model group were significantly increased,while intervention of traditional Chinese medicine inhibited TGF-β1 and Smad2/3 protein positive expression induced by Si O2,and the expression of TGF-β1 and S
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