kruppel样因子15在压力超负荷所致心肌重构血管生成中的作用及机制  

Impacts and mechanisms of kruppel like factor 15 in pressure overload induced cardiac remodeling and angiogenesis in rats

作　　者：余杨[1] 邹书帆 马杰[1] 陈林[1] 

机构地区：[1]第三军医大学新桥医院心外科,重庆400037

出　　处：《中华心血管病杂志》2015年第2期162-166,共5页Chinese Journal of Cardiology

基　　金：国家自然科学基金（81170216）

摘　　要：目的 探讨在心脏压力超负荷引起心肌重构过程中血管生成的动态变化,及心肌成纤维细胞产生的细胞因子kruppel样因子15（KLF15）对血管生成的影响.方法 超负荷组大鼠通过升主动脉缩窄术在体内建立压力超负荷诱导的心肌肥厚动物模型,然后解除缩窄建立卸压力负荷模型,而对照组大鼠仅行假手术（每组大鼠均为10只）.观测大鼠心肌超负荷（3和6周）和卸负荷过程中心功能、心肌病理改变、间质血管生成及KLF15表达水平的变化.体外培养大鼠心肌成纤维细胞和血管内皮细胞,应用KLF15-shRNA重组腺病毒干扰原代成纤维细胞中KLF15的表达,建立体外血管生成的三维模型,观察KLF15对血管内皮细胞及血管生成的调控作用.结果 在体动物模型实验中,与对照组比较,超负荷组大鼠术后6周的升主动脉直径、左心室射血分数、左心室短轴缩短率、左心室收缩压较小,KLF15蛋白表达水平较低,而左心室舒张末期压力较高（P均＜0.01）,同时心肌肥大、纤维增生程度较低,新生血管密度较小;卸负荷后,上述指标的变化方向与之相反.在离体细胞模型实验中,KLF15蛋白表达水平KLF15-shRNA重组腺病毒转染心肌成纤维细胞后为4 922±430,对照病毒转染后为7 034±178（P ＜0.01）;KLF15-shRNA重组腺病毒转染组内皮细胞形成的管状结构较对照病毒短,且结构不完整.结论 心肌成纤维细胞中KLF15表达的增强能促进血管的生成,减轻压力超负荷心肌重构中心肌间质纤维化,提高心脏功能.Objective To explore the impact of kruppel like factor 15 （KLF15） on cardiac fibroblasts on angiogenesis in a pressure overload rat model.Methods Pressure overload was induced in female rats by aortic constriction for 3 and 6 weeks.After 6 weeks aortic banding,rats underwent aortic debanding for 3 or 6 weeks.Sham rats were observed for 3 and 6 weeks （n =10 each）.Cardiac function,myocardial pathological changes,interstitial angiogenesis and KLF15 expression during rat myocardial overloading-unloading process were determined.Cardiac fibroblasts and vascular endothelial cells were cultured in vitro in the absence or presence of KLF15-shRNA recombinant adenovirus and the regulation effect of KLF15 on vascular endothelial cells and angiogenesis was observed on a three-dimensional angiogenesis in vitro model.Results The ascending aorta diameter,ejection fraction,fractional shortening,left ventricular systolic pressure and the KLF15 protein expression level were significantly lower but the left ventricular end-diastolic pressure was significantly higher in pressure overloaded rats than in Sham rats （all P 〈0.01） after 6 weeks.At the same time,increased myocardial hypertrophy and fibrosis as well as reduced angiogenesis density were observed in pressure overloaded rats.These changes were significantly attenuated post aortic debanding.In vitro,KLF15-shRNA recombinant adenovirus transfection into cardiac fibroblasts significantly downregulated the protein expression of KLF15 compared with the control group （4 922 ±430 vs.7 034 ± 178,P 〈 0.01）.The formation of tubular structure of vascular endothelial cells was shorter after KLF15-shRNA recombinant adenovirus transfection and the structure was incomplete when compared with the control group.Conclusion Our results suggest that upregulation of KLF15 expression in myocardial fibroblasts might promote vascular generation,alleviate the myocardial interstitial fibrosis and improve cardiac function in this pressure overload rat model.

关 键 词：细胞因子类 成纤维细胞 新生血管化 病理性 

分 类 号：R542.2[医药卫生—心血管疾病]