摘要
目的探讨多西环素抑制百草枯诱导的肺纤维化的可能机制,为其临床应用提供理论依据。方法选择人肺成纤维细胞(HFL1细胞)作为细胞试验研究对象,分为对照组、PQ组、PQ+多西环素组3组。PQ组用3ml40μmol/LPQ与HFL1细胞共培养PQ+多西环素组用3ml40μmol/LPQ、3ml10mg/L多西环素与HEL1细胞供培养,用ELISA方法对转化生长因子β1(TGF-β1)、α平滑肌肌动蛋白(α-SMA)及Smad3和Smad2蛋白含量进行检测。动物组实验选用健康清洁级SD大鼠120只,随机分为对照组、PQ组、PQ+多西环素组3组,每组40只。用ELISA方法对染毒1、3、7、14、21d大鼠血浆中TGF-β1、α-SMA、Smad3和Smad2蛋白含量进行检测。用WesternBlot方法对21d大鼠肺组织匀浆中TGF-β1,α-SMA及Smad3、Smad2蛋白的表达进行检测。HE染色观察染毒1、3、7、14、21d大鼠肺组织病理变化。结果与对照组比较,随着PQ染毒时间延长,PQ组HFL1细胞和大鼠TGF-β1、α-SMA、Smad3和Smad2蛋白含量逐渐升高,差异均有统计学意义(P<0.05)。PQ+多西环素组TGF-β1,α-SMA及Smad3、Smad2蛋白的表达各时点均明显低于PQ组,但仍高于对照组,差异均有统计学意义(P<0.05)。结论多西环素可能通过抑制TGF-β1、α-SMA、Smad3、Smad2蛋白的表达来抑制PQ诱导的肺纤维化。
Objective To investigate the possible mechanism of doxycycline inhibiting paraquat-induced pulmonary fibrosis and provide a theoretical basis for its clinical application. Methods Human lung fibroblast HFL1 cells were selected as the research object in the cell group. Divided into blank group, paraquat group, paraquat+doxycycline group. The expression of TGF-β1, a-SMA, Smad3 and Smad2 protein was detected by ELISA using 40 ml of paraquat 40 umol/L and 3 mg/L of oleic acid 10 mg/L. In the animal group, 120 healthy and clean SD rats were randomly divided into three groups: blank group, paraquat group, paraquat+doxycycline group. The expression of TGF-β1, a-SMA, Smad3 and Smad2 protein in lung tissue of mice at 1 day, 3 days, 7 days, 14 days and 21 days was detected by Elisa method. The expression of TGF-β1, a-SMA, Smad3 and Smad2 protein in lung tissue of 21-day mice was detected by Western Blotting. The pathological changes of lung tissue were observed by HE staining for 1 day, 3 days, 7 days, 14 days and 21 days. Results In the cell group experiment, the expression of TGF-β1, a-SMA, Smad3 and Smad2 protein increased gradually with paraquat in the paraquat group, and the expression of TGF-β1, a-SMA, Smad3 and Smad2 protein was significantly higher than that in the blank group. The difference was statistically significant (P<0.05). The expressions of TGF-β1, a-SMA, Smad3 and Smad2 in the paraquat+doxycycline group were significantly lower than those in the paraquat group, but still higher than the blank group, the difference was statistically significant (P<0.05). Conclusion Doxycycline inhibits paraquat-induced pulmonary fibrosis by inhibiting the expression of TGF-β1, a-SMA and Smad3, Smad2 proteins.
作者
周滟如
庞昶
陈思露
唐晓芳
Zhou Yanru;Pang Chang;Chen Silu;Tang Xiaofang(Shenyang Medical College, Shenyang 110002, China;The Sencond Affiliated Hospital of Shenyang Medical College, Shenyang 110001, China)
出处
《中华劳动卫生职业病杂志》
CAS
CSCD
北大核心
2019年第5期337-341,共5页
Chinese Journal of Industrial Hygiene and Occupational Diseases
基金
沈阳医学院大学生科研创新项目(20189026)
辽宁省大学生科研创新项目(201810164014).
关键词
多西环素
百草枯
肺纤维化
机制研究
Doxycycline
Paraquat
Pulmonary fibrosis
Mechanism study
