白细胞介素-6/糖蛋白130/转录激活因子3通路在百草枯诱导小鼠急性肺损伤中的作用机制  

Study on the role of IL-6/gp130/STAT3 pathway in paraquat-induced acute lung injury in mice

作　　者：王念[1] 唐泽[1] 蒋世双 苟小红[1] 魏纯玲 陶武[1] Wang Nian;Tang Ze;Jiang Shi-shuang;Gou Xiao-hong;Wei Chun-ling;Tao Wu(Department of Critical Care Medicine,Yongchuan Hospital,Chongqing Medical University,Yongchuang 402160,China)

机构地区：[1]重庆医科大学附属永川医院重症医学科,重庆永川402160

出　　处：《中国急救医学》2021年第3期233-237,共5页Chinese Journal of Critical Care Medicine

基　　金：重庆市永川区科委自然科学基金(Ycstc,2016nc5008)。

摘　　要：目的基于肺特异性白细胞介素-6(IL-6)敲除小鼠研究IL-6/糖蛋白130(gp130)/转录激活因子3(STAT3)通路在百草枯(PQ)诱导急性肺损伤(ALI)中的作用。方法野生型C57BL/6J小鼠分为IL-6野生型(IL-6 WT)组、IL-6 WT+PQ组,采用Sftpc(肺表面活性蛋白C基因)-Cre^(+)小鼠与IL-6^(FLOX/FLOX)小鼠交配的方式得到肺特异性IL-6敲除小鼠并分为IL-6 KO组、IL-6 KO+PQ组,单次腹腔注射PQ诱导ALI,比较四组小鼠肺组织病理改变、肺泡动脉氧分压差(PA-aO_(2))、肺组织湿/干质量比值(W/D)、IL-6/gp130/STAT3通路、核转录因子-κB(NF-κB) p65、肿瘤坏死因子-α(TNF-α)及白细胞介素-1β(IL-1β)的差异。结果与IL-6 WT组比较,IL-6 WT+PQ组小鼠肺组织出现了典型的ALI病理改变,肺组织胞浆蛋白中IL-6、gp130、p-STAT3、TNF-α、IL-1β表达水平及胞核蛋白中NF-κB p65的表达水平、PA-aO_(2)、W/D明显增加(P <0.05);与IL-6 WT+PQ组比较,IL-6 KO+PQ组小鼠肺组织病理改变明显改善,肺组织胞浆蛋白中IL-6、gp130、p-STAT3、TNF-α、IL-1β的表达水平及胞核蛋白中NF-κB p65的表达水平、PA-aO_(2)、W/D明显降低(P <0.05)。结论 IL-6/gp130/STAT3通路激活与PQ诱导ALI有关。Objective To study the role of interleukin-6( IL-6)/gp130/signal transduction and activator of transcription 3( STAT3) pathway in paraquat( PQ)-induced acute lung injury( ALI)based on lung specific IL-6 knockout mice. Methods Wild type C57 BL/6 J mice were divided into IL-6 WT group and IL-6 WT + PQ group. Lung specific IL-6 knockout mice were obtained by copulation of Sftpc-Cre^(+) mice with IL-6^(FLOX/FLOX)mice and divided into IL-6 KO group and IL-6 KO + PQ group. Then ALI was induced by a single intraperitoneal injection of PQ. The differences of pathological changes of lung tissue,alveolar-arterial oxygen partial pressure difference( PA-aO_(2)),the wet/dry weight ratio( W/D) of lung tissue,IL-6/gp130/STAT3 pathway,nuclear factor-κB p65( NF-κB p65),tumor necrosis factor-α( TNF-α) and interleukin-1β( IL-1β) among 4 groups were compared. Results Compared with the IL-6 WT group,the lung tissue showed typical ALI pathological changes,and the expression levels of IL-6,gp130,p-STAT3,TNF-α,IL-1β,NF-κB p65,PA-aO_(2),W/D ratio significantly increased in IL-6 WT + PQ group( P < 0. 05). Compared with IL-6 WT + PQ group,the pathological changes of lung tissue significantly improved,and the expression levels of IL-6,gp130,p-STAT3,TNF-α,IL-1β,NF-κB p65,PA-aO_(2) and W/D ratio significantly decreased in IL-6 KO + PQ group( P < 0. 05). Conclusions The activation of IL-6/gp130/STAT3 pathway is related to PQ-induced ALI.

关 键 词：百草枯(PQ) 急性肺损伤(ALI) 白细胞介素-6(IL-6) 基因敲除 糖蛋白130(gp130) 磷酸化信号传导转录激活因子3(p-STAT3) 

分 类 号：R595.4[医药卫生—内科学] R563[医药卫生—临床医学]