KLF15基因对压力超负荷所致心肌纤维化的调控作用  

The Kriippel-like factor 15 inhibits myocardial fibrosis in a rat model of left ventricular pressure overload

作　　者：余杨[1] 邹书帆 马杰[1] 陈林[1] 

机构地区：[1]中国人民解放军第三军医大学附属新桥医院心血管外科,重庆400037

出　　处：《中华胸心血管外科杂志》2015年第7期415-418,共4页Chinese Journal of Thoracic and Cardiovascular Surgery

基　　金：国家自然科学基金面上项目（81170216）

摘　　要：目的探讨Krtippel样因子15（KLF15）基因对左心室压力超负荷致心肌纤维化的调控作用，及其分子作用机制。方法非人工通气条件下，建立大鼠主动脉瓣上缩窄致压力超负荷心肌肥厚、纤维化动物模型，随后解除缩窄制作卸压力负荷模型，观察各超负荷-卸负荷相应时间点，大鼠心脏超声心动图和心肌间质纤维化转归特征，及KLF15、转移生长因子β（TGF-β）、结缔组织生长因子（CTGF）、心肌素相关蛋白A（MRTF-A）的蛋白表达水平变化。结果成功利用SD大鼠在非人工通气条件下完成升主动脉缩窄及松解手术。与假手术组比较，主动脉瓣上缩窄后大鼠心肌组织Ⅰ、Ⅲ型胶原纤维含量、TGF-β、CTGF及MRTF-A的蛋白表达水平明显增加，KLF15的蛋白表达水平明显减低（P〈0．05），心肌肥厚纤维化加剧，且随缩窄时间延长，各值有逐渐增加趋势（P〈0．05）；卸负荷后，上述各指标变化恰好相反，越早去缩窄，改善越显著，各值间差异均有显著性（P〈0．05）。结论KLF15通过反馈调节TGF-β，抑制CTGF及MRTF-A表达，从而减轻压力超负荷所致心肌间质纤维化。Objective Based on animal model of left ventricular pressure overload induced cardiac fibrosis, to investigate the specific role and molecular mechanism of KLF15 gene in this process. Methods To establish rat animal model of pressure overload induced cardiac hypertrophy by aortic coarctatiou under non artificial ventilation conditions, and then release the constriction, to observe the rat heart color Doppler images, myocardial interstitial fibrosis features and protein expression level changes of KLF15, Transforming growth factor-β （ TGF-β ）, Connective tissue growth factor （ CTGF）, Myocardin-related transcription factor A（MRTF-A） in overload - unload corresponding time points. Results We successfully completed aortic banding and debanding operations by use of SD rats without artificial ventilation. Through color Doppler echocardiography detection, from images to know： the effect of constriction and loosening is definite. The expression of collagen type Ⅰ, collagen type Ⅲ, TGF-β, CTGF, MRTF-A were significantly higher and myocardial hypertrophy was aggravated but the KLF15 protein expression level was significantly lower in pressure overloaded rats than in Sham rats（ all P 〈 0.05 ）. All values were in an increasing tendency with the constrictive time prolonged（ P 〈0.05 ）. The response to unloading was opposite, the sooner to loose the better to the recovery to normal. The differences of indicators are very notable （ P 〈 0. 05 ）. Conclusion By feedback regulation TGF-β, KLF15 inhibited the effect of CTGF and MRTF-A, reducing myocardial interstitial fibrosis.

关 键 词：Krtippel样因子15 压力超负荷-卸负荷 动物模型 心肌间质纤维化 

分 类 号：R542.2[医药卫生—心血管疾病]