| 张小雷.NEAT1/miR-27b轴促进LPS诱导ARDS小鼠肺损伤和炎症.[J].中南医学科学杂志.,2025,(2):205-210. |
| NEAT1/miR-27b轴促进LPS诱导ARDS小鼠肺损伤和炎症 |
| NEAT1/miR-27b axis promotes LPS-induced lung injury and inflammation in ARDS mice |
| 投稿时间：2023-04-03 修订日期：2024-03-28 |
| DOI：10.15972/j.cnki.43-1509/r.2025.02.004 |
| 中文关键词: lncRNA NEAT1 miR-27b Nrf2 急性呼吸窘迫综合征 小鼠 [ |
| 英文关键词:lncRNA NEAT1 miR-27b Nrf2 ARDS mice |
| 基金项目:湖南省创新型省份建设专项(S2021JJKWLH0129) |
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| 中文摘要: |
| 目的探讨长链非编码RNA(long non-coding RNA,lncRNA)核富集丰富转录本1(nuclear-enriched abundant transcript 1,NEAT1)对LPS诱导的急性呼吸窘迫综合征(ARDS)小鼠肺损伤和炎症的影响机制。 方法将40只雄性C57BL/6小鼠随机均分为对照组、ARDS组、腺病毒对照(sh-NC)组和sh-NEAT1序列的重组腺病毒(sh-NEAT1)组。除对照组外,其他组建立ARDS模型。采用qRT-PCR、HE染色、TUNEL法分别检测各组肺组织NEAT1表达水平、组织损伤、细胞凋亡情况。采用酶联免疫吸附法检测各组肺组织肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、IL-10的表达水平。将人肺上皮细胞系小气道上皮细胞(SAEC)分为正常组、LPS组、LPS+sh-NEAT1组、LPS+sh-NEAT1+miR-27b抑制剂组。采用CCK-8法检测各组细胞活力,采用流式细胞术检测细胞凋亡率。采用双荧光素酶报告基因评估NEAT1、miR-27b、核因子红系2相关因子2(Nrf2)之间的相互作用。 结果在LPS诱导的ARDS小鼠模型和SAEC中,NEAT1表达升高(P＜0.05)。sh-NEAT1导致细胞活力增加和细胞凋亡减少,从而保护细胞免受LPS诱导的细胞损伤。sh-NEAT1抑制LPS诱导的中性粒细胞数量、髓过氧化物酶活性以及炎症细胞因子IL-6和TNF-α水平。沉默miR-27b逆转了sh-NEAT1对LPS诱导的SAEC损伤。sh-NEAT1降低了LPS诱导SAEC中Nrf2的表达。sh-NEAT1与miR-27b抑制剂的共转染逆转了sh-NEAT1对Nrf2的表达。 结论NEAT1促进LPS诱导ARDS肺损伤和炎症,可能与通过抑制miR-27b,上调Nrf2有关。 |
| 英文摘要: |
| AimTo investigate the role and mechanism of long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) in LPS-induced lung injury and inflammation in acute respiratory distress syndrome (ARDS). Methods40 C57BL/6 mice were randomly divided into control group, ARDS group, sh-NC group and sh-NEAT1 group. ARDS models were established in all groups except the control group. qRT-PCR, HE staining, TUNEL were used to detect the expression level of NEAT1, tissue damage and apoptotic cells in lung tissue. The expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 in lung tissue were detected by enzyme-linked immunosorbent assay. Small airway epithelial cells (SAEC) of human lung epithelial cell line were divided into normal group, LPS group, LPS+sh-NEAT1 group and LPS+sh-NEAT1+miR-27b inhibitor group. Cell viability was detected by CCK-8 method, and apoptosis was detected by flow cytometry. The interactions between NEAT1, miR-27b and nuclear factor-erythroid-2-related factor 2 (Nrf2) were assessed by using dual luciferase reporter gene assay. ResultsThe expression level of NEAT1 was increased in LPS-induced ARDS mouse model and SAEC. sh-NEAT1 resulted in increased cell viability and decreased apoptosis, leading to protective effect against LPS-induced cell damage. sh-NEAT1 inhibited LPS-induced neutrophil number, myeloperoxidase activity, and production of inflammatory cytokines IL-6, and TNF-α. The silencing of miR-27b reversed the effects of sh-NEAT1 on LPS-induced damage in SAEC. sh-NEAT1 reduced the expression level of Nrf2 in LPS-induced SAEC. Co-transfection of sh-NEAT1 with miR-27b inhibitor reversed the effect of sh-MINCR on the expression of Nrf2. ConclusionNEAT1 promotes LPS-induced lung injury and inflammation in ARDS, which may be related to the inhibition of miR-27b and up-regulat on of Nrf2. |
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