摘 要: 目的 探讨法尼醇C受体激动剂奥贝胆酸抑制百草枯诱导的肺纤维化机制,为其临床应用提供理论依据。方法 细胞实验选择人肺成纤维细胞(HFL1细胞),分为空白组、百草枯组、百草枯+奥贝胆酸组,染毒1 d后采用Elisa方法对转化生长因子β1(TGF-β1),a-平滑肌肌动蛋白(a-SMA)及Smad3、Smad2蛋白的表达进行检测。动物实验选用健康清洁级SD大鼠60只,随机分为空白组、百草枯组、百草枯+奥贝胆酸组,采用Elisa方法对染毒第1、3、7、14、21天大鼠血浆中TGF-β1、 a-SMA及Smad3、Smad2蛋白的表达进行检测。采用Western Blotting方法对第21天大鼠肺组织中TGF-β1、a-SMA及Smad3、Smad2蛋白的表达进行检测。HE染色观察第1、3、7、14、21天大鼠肺组织病理变化。结果 细胞实验和动物实验中百草枯组均随着中毒时间延长,TGF-β1、a-SMA及Smad3、Smad2蛋白的表达逐渐升高,各时点均明显高于空白组(P<0.05)。百草枯+奥贝胆酸组TGF-β1、a-SMA及Smad3、Smad2蛋白的表达各时点均明显低于百草枯组,但仍高于空白组,差异有统计学意义(P<0.05)。结论 奥贝胆酸可通过抑制TGF-β1、a-SMA及Smad3、Smad2蛋白的表达来抑制百草枯诱导的肺纤维化。 |
关键词: 奥贝胆酸 法尼醇C受体(FXR)激动剂 百草枯 肺纤维化 机制 |
中图分类号: A
文献标识码: R994
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基金项目: 辽宁省自然科学基金(编号:20180550506) |
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Study on mechanism of inhibition of paraquat-induced pulmonary fibrosis by FXR agonist obeticholic acid |
PANG Chang,FENG Yu-meng,ZHU Li-na,SHEN Chun-jian
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(Second Affiliated Hospital of Shenyang Medical College, Shenyang 110002, China)
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Abstract: Objective To investigate the mechanism of inhibition of paraquat-induced pulmonary fibrosis by the FXR agonist obetichoic acid, thereby provide theoretical basis for its clinical application. Methods Human lung fibroblasts (HFL1 cells) were divided into blank, paraquat and paraquat+aubecholic three groups. One day after exposure, the expression of TGF-β1, a-SMA (smooth muscle actin), Smad3 and Smad2 proteins were detected by Elisa . 60 healthy and clean SD rats were randomly divided into blank group, paraquat group,paraquat+obetichoic acid group; Elisa method was also used to detect the expression of TGF-β1, a-SMA, Smad3 and Smad2 proteins in the plasma of mice at day 1, 3, 7, 14 and 21 after exposure, Western blotting was used to detect the expression of TGF-β1, a-SMA, Smad3 and Smad2 proteins in lung tissues of the 21th day mice, HE staining was used to observe the histopathological changes in lung tissues of mice at 1 day, 3 days, 7 days, 14 days, and 21 days after exposure.Results The results showed that both in the cell and animal experiment, the expression of TGF-β1, a-SMA, Smad3 and Smad2 proteins in paraquat group were gradually increased with the prolongation of paraquat exposure, which all were significantly higher than that of the blanks at each time point(P<0.05). While the expressions of TGF-β1, a-SMA, Smad3 and Smad2 proteins of paraquat+obetichoic acid group were significantly lower than that of paraquat group at each time point, but still higher than that in blank group (P<0.05). Conclusion The results suggested that the mechanism of obetichoic acid inhibiting paraquat-induced pulmonary fibrosis might be by the way of inhibiting the expression of TGF-β1, a-SMA and Smad3 and Smad2 proteins. |
Keywords: obeticholic acid farnesol X-receptor (FXR) agonist paraquat pulmonary fibrosis mechanism |