Department of Critical Care Medicine, Dongying People's Hospital, Dongying, Shandong Province, China.
Eur Rev Med Pharmacol Sci. 2018 Dec;22(23):8438-8446. doi: 10.26355/eurrev_201812_16543.
To explore the regulatory effects of microRNA-218 on lung tissue of rats with acute lung injury (ALI) and its underlying mechanism.
A total of 32 Sprague Dawley (SD) rats were randomly divided into control group, lung injury group and microRNA-218 treatment group. The in vitro lung injury model was established by injections of lipopolysaccharide (LPS), PGN (peptidoglycan) and IgG IC (immune complex). Polymerase Chain Reaction (PCR) was performed to detect the expression of microRNA-218 in lung tissues of ALI rats. Enzyme-Linked Immunosorbent Assay (ELISA) was used to measure the level of cytokine secretion in ALI rats. The activity and expression level of nuclear factor-kappa B (NF-κB) in MH-S and RA264.7 cells were determined by Luciferase activity assay and Western blot, respectively.
MicroRNA-218 was significantly down-regulated in bleomycin and IgG IC-induced lung injury rat model, as well as in cells treated with LPS, PGN and IgG IC. Inflammatory factors, including TNF-α, IL-1b, and IL-6, also showed increased in vivo and in vitro expressions. Besides, the overexpression of microRNA-218 inhibited the secretion of inflammatory factors. PCR analysis and Luciferase activity assay indicated that the expressions of RUNX2 and BIRC3 were down-regulated by microRNA-218 in MH-S and RA264.7 cells. Subsequent studies on mechanisms demonstrated that microRNA-218 inhibited the activity of the NF-κB pathway.
The expression of microRNA-218 markedly decreased in lung tissue of ALI rats, while the expression of inflammatory cytokines showed a remarkable increase, which might be related to the activation of RUNX2 and NF-κB.
探讨 microRNA-218 对急性肺损伤（ALI）大鼠肺组织的调控作用及其机制。
32 只 Sprague Dawley（SD）大鼠随机分为对照组、肺损伤组和 microRNA-218 处理组。采用脂多糖（LPS）、肽聚糖（PGN）和免疫复合物（IgG IC）注射建立大鼠体外肺损伤模型。采用聚合酶链反应（PCR）检测 ALI 大鼠肺组织中 microRNA-218 的表达。酶联免疫吸附试验（ELISA）检测 ALI 大鼠细胞因子分泌水平。采用荧光素酶活性检测和 Western blot 分别检测 MH-S 和 RA264.7 细胞中核因子-κB（NF-κB）的活性和表达水平。
博来霉素和 IgG IC 诱导的肺损伤大鼠模型以及 LPS、PGN 和 IgG IC 处理的细胞中，microRNA-218 表达明显下调。TNF-α、IL-1b 和 IL-6 等炎症因子的表达也呈体内和体外增加趋势。此外，microRNA-218 的过表达抑制了炎症因子的分泌。PCR 分析和荧光素酶活性检测表明，microRNA-218 下调了 MH-S 和 RA264.7 细胞中 RUNX2 和 BIRC3 的表达。随后的机制研究表明，microRNA-218 抑制了 NF-κB 通路的活性。
ALI 大鼠肺组织中 microRNA-218 的表达明显下调，而炎症细胞因子的表达明显增加，这可能与 RUNX2 和 NF-κB 的激活有关。
