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《中华肺部疾病杂志》[ISSN:1006-6977/CN:61-1281/TN]

卷:

期数:

2024年05期

页码:

696-700

栏目:

论著

出版日期:

2024-10-25

文章信息/Info

Title:

miR-200b-3p suppressed the edema in seawater aspiration-induced ALI via inhibition the expression of HIF-1α

作者:

张敏龙¹; 2; 杨翠平¹; 王 博¹; 崔云杰¹; 3; 金发光²

100091 北京,解放军总医院第八医学中心呼吸与危重症医学部¹
710038 西安,空军军医大学唐都医院呼吸科²
025250 赤峰,内蒙古赤峰市林西县医院呼吸科³

Author(s):

Zhang Minlong¹; 2;  Yang Cuiping¹;  Wang Bo¹;  Cui Yunjie¹; 3;  Jin Faguang².

¹Department of Respiratory and Critical Care Medicine, the 8th Medical Center, PLA General Hospital, Beijing 100091, China; ²Department of Respiratory, Tangdu Hospital, Air Force Military Medical University, Xi'an 710038, China; ³Department of Respiratory, Linxi Hospital, Chifeng 025250, ChinA

关键词:

急性肺损伤;  海水;  低氧诱导因子-1/血管内皮生长因子通路;  miR-200b-3p

Keywords:

Acute lung injury;  Seawater;  Hypoxia inducible factor-1/vascular endothelial growth factor pathway;  miR-200b-3p

分类号:

R563

DOI:

10.3877/cma.j.issn.1674-6902.2024.05.005

摘要:

目的 分析miR-200b-3p在海水吸入性急性肺损伤(acute lung injury, ALI)中的作用及机制。 方法 选取32只健康SD大鼠,分为空白对照组、海水刺激组、miR-200b-3p antagomir预处理组和antag NC预处理组,每组8只,构建海水吸入性肺损伤大鼠及大鼠肺微血管内皮细胞(rat pulmonary microvascular endothelial cells, RPMVECs)模型。观察肺组织湿干比(W/D)、伊文思蓝法检测肺微血管通透性,Western blot检测低氧诱导因子-1(hypoxia inducible factor-1, HIF-1α)及血管内皮生长因子(vascular endothelial growth factor, VEGF)的表达变化,采用双荧光素酶报告基因实验验证HIF-1α和miR-200b-3p的作用关系。 结果 海水干预4 h后,大鼠肺组织湿干比(W/D)及通透性明显增加,在肺组织及细胞模型中miR-200b-3p表达明显增高,HIF-1α表达出现升高,VEGF表达同时也出现上升。而抑制miR-200b-3p的表达后,肺水肿得到明显的减轻,肺组织及细胞模型中HIF-1α表达出现下降,VEGF表达也出现下降。双荧光素酶报告基因验证miR-200b-3p直接靶向作用于HIF-1α。与空白对照组对比,海水刺激组大鼠肺组织中HIF-1α及VEGF表达增加,RPMVECs细胞中HIF-1α及VEGF表达增加。结论 增加表达的miR-200b-3p在海水吸入性肺损伤肺组织水肿的发展中起到关键作用,这种作用是通过调节HIF-1α/VEGF通路形成的。

Abstract:

Objective To analyze the role and mechanism of miR-200b-3p in seawater inhalation acute lung injury(ALI). Methods Thirty-two healthy SD rats were selected and divided into blank control group, seawater stimulation group, miR-200b-3p antagomir pretreatment group and antag NC pretreatment group, with 8 rats in each group. The rat pulmonary microvascular endothelial cells(RPMVECs)model of seawater inhalation lung injury and rat pulmonary microvascular endothelial cells were constructed. Wet-dry ratio(W/D)of lung tissue was observed, and microvascular permeability of lung was detected by Evans blue method. Western blot analysis of the expression of -hypoxia inducible factor-1(HIF-1α)and vascular endothelial growth factor(VEGF)were detected. Dual luciferase reporter gene assay was used to verify the relationship between HIF-1α and miR-200b-3p. Results After seawater treatment for 4 h, the wet-dry ratio(W/D)and permeability of lung tissue were significantly increased, and the expression of miR-200b-3p, HIF-1α and VEGF were significantly increased in lung tissue and cell models. However, inhibition of the expression of miR-200b-3p significantly alleviated pulmonary edema, the expression of HIF-1α and VEGF were decreased in lung tissues and cell models. Dual luciferase reporter gene verified that miR-200b-3p directly targeted HIF-1α. Compared with blank control group, the expressions of HIF-1α and VEGF in lung tissue and HIF-1α and VEGF in RPMVECs cells were increased in seawater stimulated group. Conclusion Increased expression of miR-200b-3p plays a key role in the development of pulmonary edema induced by seawater aspiration injury, which is mediated by the HIF-1α/VEGF pathway.

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备注/Memo

备注/Memo:

基金项目: 解放军总医院第八医学中心国科金配套基金(QN202211004)
通信作者: 金发光, Email: jinfag@fmmu.edu.cn

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更新日期/Last Update: 2024-10-25