miR-21通过下调ADAMTS-1表达促进大鼠肺纤维化

发布时间：2018-05-15 08:52

本文选题：微小RNA(miR-) + 肺纤维化　；参考：《细胞与分子免疫学杂志》2016年12期

【摘要】：目的探讨微小RNA21(miR-21)对博莱霉素诱导的大鼠肺纤维化的影响及相关机制。方法收集特发性肺纤维化(IPF)患者及正常人的外周血各20份,采用荧光实时定量PCR检测miR-21表达。将45只SD大鼠随机分为对照组、miR-21激动剂(miR-21agomir)和miR-21拮抗剂(miR-21antagomir)组,每组15只。经气管内注入博莱霉素A5建立肺纤维化模型后,分别给予生理盐水、miR21 agomir、miR21 antagomir尾静脉注射,第28天处死所有大鼠。取出肺组织,行HE和Masson染色,通过荧光实时定量PCR和Western blot法分别检测含1型血小板结合蛋白基序的解聚蛋白样金属蛋白酶(ADAMTS-1)、1型胶原蛋白(Col1)、Col3 mRNA与蛋白表达,分离血清,ELISA检测血清1型前胶原蛋白羧基端前肽(P1CP)和3型前胶原蛋白氨基端前肽(P3NP)的含量。结果 IPF患者外周血miR-21表达水平明显高于正常人。miR-21 agomir组大鼠肺泡炎和肺纤维化程度明显重于对照组,而miR-21 antagomir组大鼠肺泡炎和肺纤维化程度显著轻于对照组。与对照组相比,miR-21 agomir组ADAMTS-1mRNA与蛋白表达水平降低,Col1、Col3的mRNA与蛋白表达水平及血清P1CP、P3NP水平均增加。但miR-21 antagomir组ADAMTS-1 mRNA与蛋白表达水平较对照组升高,Col1、Col3的mRNA与蛋白表达水平及血清P1CP、P3NP含量较对照组减少。结论 miR-21促进博莱霉素诱导的大鼠肺纤维化进展,其机制可能与下调ADAMTS-1表达及随后增加肺组织Col1、Col3含量有关。
[Abstract]:Objective to investigate the effects of minimal RNA21 miR-21 on bleomycin induced pulmonary fibrosis in rats and its related mechanisms. Methods 20 patients with idiopathic pulmonary fibrosis (IPF) and 20 normal controls were collected. The expression of miR-21 was detected by fluorescence real time quantitative PCR. Forty-five SD rats were randomly divided into control group (n = 15) and miR-21 antagonist group (n = 15). The pulmonary fibrosis model was established by intratracheal injection of bleomycin A _ 5. All the rats were killed on the 28th day after intravenous injection of normal saline miR21 agomirir-miR21 antagomir. Lung tissue was taken out and stained with HE and Masson. The expression of ADAMTS-1 collagen type 1 collagen was detected by real-time quantitative PCR and Western blot, respectively. Serum procollagen type 1 (P1CPP) and type 3 procollagen amino terminal propeptide (P3NPP) were detected by Elisa. Results the expression of miR-21 in peripheral blood of patients with IPF was significantly higher than that of normal persons. The degree of alveolitis and pulmonary fibrosis in the group of miR-21 agomir was significantly higher than that in the control group, while the degree of alveolitis and pulmonary fibrosis in the group of miR-21 antagomir was significantly lower than that in the control group. Compared with the control group, the expression of ADAMTS-1mRNA and protein in the miR-21 agomir group was significantly lower than that in the control group. However, the expression level of ADAMTS-1 mRNA and protein in miR-21 antagomir group was significantly higher than that in control group. The expression of mRNA and protein in Col1C Col3 and the level of P1CPP P3NP in serum were lower in miR-21 antagomir group than in control group. Conclusion miR-21 can promote the progression of pulmonary fibrosis induced by bleomycin in rats. The mechanism may be related to the down-regulation of ADAMTS-1 expression and the subsequent increase of Col1c Col3 content in lung tissue.
【作者单位】：湖南医药学院临床医学院;湖南医药学院第一附属医院呼吸内科;怀化市第一人民医院呼吸内科;南华大学附属第一医院呼吸内科;
【基金】：湖南省教育厅资助优秀青年科研项目(14B142)
【分类号】：R563

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