Department of Emergency Center, The First People's Hospital of Wenling, No.333 Chuan'an South Road, Chengxi Street, Zhejiang Province, 317500, Wenling, China.
J Bioenerg Biomembr. 2020 Aug;52(4):229-236. doi: 10.1007/s10863-020-09839-3. Epub 2020 Jun 2.
This study aimed to explore the role of miR-146b-3p in acute respiratory distress syndrome in septic mice. Ten mice were randomly selected as normal group (n = 10, without any treatment) and 60 septic mice with acute respiratory distress syndrome were divided into model group (n = 10, without any treatment), negative control (NC) mimic group (n = 10, injected with NC mimic), miR-146b-3p mimic group (n = 10, injected with miR-146b-3p mimic), si-NC group (n = 10, injected with PI3Kγ siRNA NC), si-PI3Kγ group (n = 10, injected with PI3Kγ silencing plasmid), and miR-146b-3p mimic + oe-PI3Kγ group (n = 10, injected with miR-146b-3p mimic + PI3Kγ overexpression plasmid). We found that miR-146b-3p negatively regulated PI3Kγ. Compared with normal group, model mice had decreased expression of miR-146b-3p, increased expressions of PI3Kγ, p-AKT, ASC, NLRP3 and Caspase-1 proteins, higher W/D ratio, and more serum IL-1β and IL-18 content (all P < 0.05). All indicators in miR-146b-3p mimic group and si-PI3Kγ group were significantly improved as compared to model group (all P < 0.05). Over-expression of PI3Kγ could weaken the treatment effect of miR-146b-3p mimic in model mice. Therefore, up-regulation of miR-146b-3p can inhibit PI3K/AKT signaling pathway to improve acute respiratory distress syndrome in septic mice.
本研究旨在探讨 miR-146b-3p 在脓毒症小鼠急性呼吸窘迫综合征中的作用。随机选取 10 只小鼠作为正常组(n=10,未进行任何处理),60 只脓毒症合并急性呼吸窘迫综合征小鼠分为模型组(n=10,未进行任何处理)、阴性对照(NC) mimic 组(n=10,注射 NC mimic)、miR-146b-3p mimic 组(n=10,注射 miR-146b-3p mimic)、si-NC 组(n=10,注射 PI3Kγ siRNA NC)、si-PI3Kγ 组(n=10,注射 PI3Kγ 沉默质粒)和 miR-146b-3p mimic+oe-PI3Kγ 组(n=10,注射 miR-146b-3p mimic+PI3Kγ 过表达质粒)。结果发现,miR-146b-3p 负调控 PI3Kγ。与正常组相比,模型组小鼠 miR-146b-3p 表达降低,PI3Kγ、p-AKT、ASC、NLRP3 和 Caspase-1 蛋白表达升高,W/D 比值更高,血清中 IL-1β 和 IL-18 含量更高(均 P<0.05)。miR-146b-3p mimic 组和 si-PI3Kγ 组的所有指标与模型组相比均显著改善(均 P<0.05)。过表达 PI3Kγ 可减弱 miR-146b-3p 模拟物在模型小鼠中的治疗作用。因此,上调 miR-146b-3p 可抑制 PI3K/AKT 信号通路,改善脓毒症小鼠急性呼吸窘迫综合征。