Jin Li-Yan, Li Cong-Feng, Zhu Guang-Fa, Wu Chun-Ting, Wang Jun, Yan Shu-Feng
Department of Infectious Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, P.R. China.
Department of Respiratory and Critical Care Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, P.R. China.
Mol Med Rep. 2014 Aug;10(2):631-7. doi: 10.3892/mmr.2014.2299. Epub 2014 Jun 5.
The aim of the present study was to explore the protective effect of small interfering RNA (siRNA) against nuclear factor κB (NF-κB) p65 on sepsis-induced acute lung injury (ALI) in mice. In total, 70 male Kunming mice were randomly divided into a healthy control group, a sepsis group, a specific interfering group and a scrambled control group (Sc), and the latter three groups were divided into post-operational 6 and 12 h subgroups, each of which consisted of 10 mice. The mice were administered with NF-κB siRNA, scrambled siRNA and normal saline via tail vein injection. Following 1 h, a mouse model of septic ALI was produced by cecal ligation and puncture (CLP) in the two siRNA groups and the sepsis control group. At 6 and 12 h post‑operation, the experimental mice were sacrificed and the lung tissue samples were collected. Histopathological changes, wet/dry ratio of lung weight, NF-κB protein and NF-κB p65 mRNA levels, matrix metalloproteinase-9 (MMP-9) mRNA and protein activity were detected. Compared with the sepsis group and the Sc at the corresponding time, the expression levels of NF-κB p65 mRNA, the lung injury of experimental mice, the wet/dry ratio and the levels of MMP-9 mRNA and protein activity decreased, and significant differences were observed at 6 h post-operation (P<0.05). RNA interference against NF-κB p65 was able to decrease the expression of NF-κB and further inhibit the early phasic excessive inflammatory reaction in sepsis, which may alleviate ALI.
本研究旨在探讨小干扰RNA(siRNA)靶向核因子κB(NF-κB)p65对小鼠脓毒症诱导的急性肺损伤(ALI)的保护作用。将70只雄性昆明小鼠随机分为健康对照组、脓毒症组、特异性干扰组和乱序对照组(Sc),后三组再分为术后6小时和12小时亚组,每组10只。通过尾静脉注射给予小鼠NF-κB siRNA、乱序siRNA和生理盐水。1小时后,在两个siRNA组和脓毒症对照组中通过盲肠结扎穿孔术(CLP)建立脓毒症ALI小鼠模型。术后6小时和12小时,处死实验小鼠并收集肺组织样本。检测组织病理学变化、肺组织湿/干重比、NF-κB蛋白和NF-κB p65 mRNA水平、基质金属蛋白酶-9(MMP-9)mRNA及蛋白活性。与相应时间的脓毒症组和Sc组相比,实验小鼠的NF-κB p65 mRNA表达水平、肺损伤、湿/干重比以及MMP-9 mRNA和蛋白活性水平均降低,术后6小时差异有统计学意义(P<0.05)。针对NF-κB p65的RNA干扰能够降低NF-κB的表达,并进一步抑制脓毒症早期过度的炎症反应,可能减轻ALI。