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

Abstract:

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⁃1 β），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⁃α and 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⁃α and 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.

Key words:

chronic heart failure, interleukin ?8, signal transducer and activator of transcription 3, cardiac function, myocardial specific gene knockout