特异性敲除心肌白细胞介素⁃8抑制信号转导及转录激活蛋白3活化改善慢性心力衰竭小鼠心功能及炎症反应  

Specific myocardial IL⁃8 knockout improves cardiac function and inflammatory response in mice with chronic heart failure via inhibiting STAT3 activation

作　　者：恩歌 陈少杰[2] 刘阳 林祥灿 EN Ge;CHEN Shaojie;LIU Yang;LIN Xiangcan(Department of Cardiology,PKUCare CNOOC Hospital,Tianjin 300452,China;不详)

机构地区：[1]天津北大医疗海洋石油医院心内科,天津300452 [2]中山大学孙逸仙纪念医院消化内科,广州510120 [3]南华大学附属第二医院心血管内科,湖南衡阳421000

出　　处：《实用医学杂志》2022年第20期2518-2523,共6页The Journal of Practical Medicine

基　　金：国家自然青年科学基金项目(编号:82103142)。

摘　　要：目的研究特异性敲除心肌白细胞介素-8(interleukin⁃8,IL⁃8)抑制信号转导及转录激活蛋白3(signal transducer and activator of transcription 3,STAT3)活化改善慢性心力衰竭(CHF)小鼠心功能及炎症反应。方法野生型(WT)雄性小鼠分为WT对照组、WT模型组,心肌特异性IL⁃8敲除(KO)雄性小鼠分为KO对照组、KO模型组,采用腹主动脉缩窄法建立CHF模型。采用超声心动图及血清中N末端脑钠肽(BNP)前体评价心功能,检测白介素⁃1β(IL⁃1β)、干扰素⁃γ(IFN⁃γ)、肿瘤坏死因子⁃α(tumor necrosis factor⁃α,TNF⁃α)的水平,IL⁃8、p⁃STAT3的表达水平。结果WT模型组心肌中出现了CHF的病理改变,心功能弱于WT对照组,IL⁃1β、IFN⁃γ、TNF⁃α的水平及IL⁃8、p⁃STAT3蛋白表达水平均高于对照组(P<0.05);特异性敲除IL⁃8并进行CHF造模,KO模型组心肌中CHF病理改变明显减轻,心肌中不表达IL⁃8,心功能优于WT模型组,IL⁃1β、IFN⁃γ、TNF⁃α的水平及p⁃STAT3的蛋白表达水平均低于WT模型组(P<0.05)。结论心肌特异性IL⁃8敲除显著改善CHF小鼠的心功能及心肌炎症反应,抑制STAT3磷酸化活化是与之相关的分子机制。Objective To study the effect of specific myocardial interleukin⁃8(IL⁃8)knockout on cardiac function and inflammatory response in mice with chronic heart failure(CHF)via inhibiting signal transducer and activator of transcription 3(STAT3).Methods Wild type(WT)male mice were divided into WT control group and WT model group.Myocardial specific IL⁃8 knockout(KO)male mice were divided into KO control group and KO model group.The CHF model was established by abdominal aortic coarctation.Four weeks after modeling,echocardiography and the levels of N⁃terminal proBNP were used to evaluate heart function,the levels of interleukin⁃1β(IL⁃1β),interferon⁃γ(IFN⁃γ),tumor necrosis factor⁃α(TNF⁃α)and the expression levels of IL⁃8 and p⁃STAT3 were detected.Results Pathological changes of CHF were found in the myocardium of WT model group,the cardiac function was weaker than that of WT model group,the levels of IL⁃1β,IFN⁃γ,TNF⁃αand the protein expression levels of IL⁃8,p⁃STAT3 in myocardium were higher than those in the control group(P<0.05).After specific IL⁃8 knockout and CHF modeled,the pathological changes of CHF in myocardium of KO model group were significantly reduced,IL⁃8 was not expressed in myocardium,the cardiac function was better than that of WT model group,the levels IL⁃1β,IFN⁃γ,TNF⁃αand the protein expression levels of p⁃STAT3 were lower than those in WT model group(P<0.05).Conclusion Myocardial specific IL⁃8 knockout significantly improved cardiac function and myocardial inflammatory response in CHF mice,the inhibition of STAT3 phosphorylation activation was a possible molecular mechanism.

关 键 词：慢性心力衰竭 白细胞介素⁃8 信号转导及转录激活蛋白3 心功能 心肌特异性基因敲除 

分 类 号：R541.6[医药卫生—心血管疾病]