白介素18在心房颤动发生中作用的实验研究

In recent years, the growing evidence shows that inflammation may be related to atrial fibrillation(AF) and inflammation may be a possible contributing factor to the initiation of AF. Studies have identified that the levels of inflammatory serum biomarkers (CRP、IL-6 and TNF-α) are elevated in patients with AF. However, the association between interleukin 18 and AF has not been reported yet. Our studies examined the expression of IL-18 in patients with AF firstly and documented the elevated level of IL-18 in AF patients. We concluded IL-18 is an independent predictor in all types of atrial fibrillation and may be superior to other inflammatory markers. Therefore we hypothesized IL-18 participating in the pathological processes of AF, but the exact mechanism of IL-18 in the initiation and perpetuation of AF remain uncertain. We are working on the project from the angle of basic animal Experiment Study. A Canine atrial fibrillation model with rapid atrial pacing can be established by injecting the exogenous IL-18, we can detect the expression of IL-18 and MyD88- NF-κB pathway of atrial myocardium during AF, and observe the effects of IL-18 on pathological and electrophysiological features of atrial muscle and the relation to other inflammatory factors. Besides, we will find the possible mechanisms and efforts of IL-18 in AF by IL-18 binding protein which was provided to interfere in advance. This study will confirm the theory that IL-18 is involved in the initiation of AF and will provide the reliable experiments evidence for the study of mechanism of AF.

近年来研究表明炎症和房颤有关，房颤患者体内肿瘤坏死因子(TNF)等炎症因子水平升高,IL-18是炎症反应中的上游调控因子，可诱导TNF等多种炎症因子产生，但IL-18与房颤的关系以前未见报道。我们研究发现房颤患者外周血中IL-18水平升高，首次报道了IL-18是房颤的独立预测因子且相关性最强，IL-18可能参与了房颤的病理过程，但是IL-18在房颤发生中的作用及机制尚不清楚。本项目拟从基础动物实验研究的角度，通过建立犬快速心房起搏房颤模型及给予外源性IL-18，检测房颤时心房肌局部IL-18等炎症因子及髓样分化因子88-核转录因子κB (MyD88- NF-κB)信号通路的表达情况，观察IL-18对心房肌组织病理及电生理特性的影响，证实IL-18参与了房颤发生的病理过程，并在此基础上初步探讨IL-18在房颤发生中的作用及可能机制，为阐明炎症在心房颤动发生、发展过程中的作用提供实验依据。

背景: 心房颤动（AF）影响总人口的1％-2％。慢性炎症在房颤发展中起重要作用，白介素-18（IL-18）是促炎细胞因子。本研究评估IL-18的单核苷酸多态性（SNPs）与房颤发生风险的相关性。.对象与方法：本研究共有243例房颤患者和160例对照者，使用MassArray系统对IL-18基因的六种常见的单核苷酸多态性进行基因分型。通过使用SAS 9.1版本分析IL-18的SNPs与房颤发生风险的相关性。.结果：IL-18的单核苷酸多态性能够降低房颤的发生风险，调整混杂因素后，差异仍然显著。尤其在rs187238位点的GC基因型和C等位基因，在rs360719位点的AG基因型和G等位基因以及在rs549908位点的GT基因型和G等位基因都能够降低房颤发生风险。与对照组相比较，房颤组患者左房内径大，射血分数低。.结论：我们的研究结果表明，IL-18的rs187238，rs360719和rs549908位点在本组研究人群中都能够降低房颤的发生风险。未来还需要进一步的研究来阐述这些SNPs对IL-8表达的影响以及在房颤发生、发展中的作用。