miR-200b对小鼠矽肺纤维化的抑制作用  

Inhibitory effect of miR-200b on silicotic fibrosis in mice

作　　者：袁翠芳 李航 熊余璐 郭梓烨 王颿 陈茹茹 郝小惠 刘和亮 郭灵丽 Yuan Cuifang;Li Hang;Xiong Yulu;Guo Ziye;Wang Fan;Chen Ruru;Hao Xiaohuie;Liu Heliang;Cuo Linglia(School of Public Health,North China University of Science and Technology,Tangshan 063210;Hebei Key Laboratory of Organ Fibrosis,Tangshan 063210)

机构地区：[1]华北理工大学公共卫生学院,唐山063210 [2]河北省器官纤维化重点实验室,唐山063210

出　　处：《安徽医科大学学报》2023年第8期1313-1316,共4页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81602814);河北省高等学校科学技术研究项目(编号:BJ2017006)。

摘　　要：目的探究微小RNA-200b(miR-200b)对二氧化硅(SiO_(2))诱导的小鼠矽肺纤维化的抑制作用。方法将24只雄性C57BL/6小鼠随机分为对照组、SiO_(2)组、SiO_(2)+agomir-NC组和SiO_(2)+miR-200b agomir组,每组6只。SiO_(2)组小鼠予以气管滴注5 mg SiO_(2)悬液,SiO_(2)+miR-200b agomir组和SiO_(2)+agomir-NC组小鼠分别在造模第1天、第7天气管滴注miR-200b模拟物(miR-200b agomir)和agomir的阴性对照(agomir-NC)。造模第14天检测小鼠肺功能后将其处死,采用HE和Masson染色观察小鼠肺组织病理变化;对支气管肺泡灌洗液(BALF)中总蛋白浓度和白细胞总数进行测定,并使用ELISA试剂盒检测小鼠BALF中转化生长因子-β1(TGF-β1)的含量。结果与对照组相比,SiO_(2)组和SiO_(2)+agomir-NC组小鼠肺内可见炎性细胞聚集且伴有胶原沉积,而SiO_(2)+miR-200b agomir组小鼠肺组织中炎症减轻、胶原沉积减少。与对照组相比,SiO_(2)组和SiO_(2)+agomir-NC组小鼠呼吸频率(f)加快、呼吸暂停(PAU)次数增加(P<0.05),呼气峰值时间比率(Rpef)降低(P<0.05),经过miR-200b agomir干预后,小鼠肺功能得到改善。此外,miR-200b agomir干预也可以有效缓解SiO_(2)刺激引起的小鼠BALF中总蛋白浓度、白细胞总数和TGF-β1含量的增加。结论miR-200b可以有效减缓矽肺小鼠肺功能下降,抑制小鼠矽肺纤维化的发生发展。Objective To explore the inhibitory effect of microRNA-200b(miR-20b)on pulmonary fibrosis in silicotic mice.Methods Male C57BL/6 mice were randomly divided into control group,SiO_(2) group,SiO,+agomir-NC group and SiO,+miR-200b agomir group,with 6 mice in each group.The mice in the SiO_(2) group were instilled intratracheally with 50μl of saline containing 5 mg SiO_(2) particles.miR-200b agomir and agomir-NC were delivered to mice in the SiO_(2)+miR-200b agomir and SiO,+agomir-NC groups respectively by intratracheal instillation on day 1 and 7 after SiO_(2) exposure.Animals were sacrificed after the lung function test on the 14th day.The pathological changes of lung tissues were observed by HE and Masson staining.Then the concentration of total proteins and the numbers of leukocytes in bronchoalveolar lavage fluid(BALF)were measured.The content of transforming growth factor-β1(TCF-β1)in BALF was detected by ELISA kit.Results Compared with the control group,inflammatory cell infiltration and collagen deposition were observed in the lungs tissues of the mice in the SiO_(2) group and the SiO_(2)+agomir-NC group,while these detrimental effects were weakened in the SiO_(2)+miR-200b agomir group.In addition,compared with the control group,the frequency(f)was accelerated and the number of Pause(PAU)increased(P<0.05),while the ratio rate of achieving peak expiatory flow(Rpef)decreased in the SiO_(2) group and the SiO_(2)+agomir-NC group(P<0.05).After miR-200b agomir intervention,the lung function of silicotic mice was improved.Moreover,miR-200b agomir intervention could also effectively alleviate the increase in the concentrations of total protein,the numbers of total leukocytes and the secretion of TGF-β1 in the BALF of mice induced by SiO_(2)stimulation.Conclusion miR-200b can effectively ameliorate the lung function of silicotic mice and inhibit the progress of fibrosis.

关 键 词：矽肺 miR-200b 纤维化 

分 类 号：R135.2[医药卫生—劳动卫生]