南京大学发本领域影响因子第一杂志论文

　　

生物通报道：来自南京大学附属鼓楼医院心脏科的研究人员获得了心肌梗死后抗心肌重建的基因治疗研究的新进展，这一研究成果公布在心血管病学杂志影响因子排名第一的《循环》（影响因子为12.755）。

领导这一研究的是南京大学附属鼓楼医院的博士生导师徐标教授，其擅长冠心病介入治疗、起搏器植入、心力衰竭的抢救、高血压病、心律失常的诊治，尤其在冠脉介入及先天性心脏病介入治疗方面具有丰富的经验。主持国家自然科学基金项目研究2项，省级科研项目10余项。发表论文70余篇，SCI收录19篇。

心肌梗塞（myocardial infarction）是冠状动脉闭塞血流中断，使部分心肌因严重的持久性缺血而发生局部坏死。临床上有剧烈而较持久的胸骨后疼痛发热、白细胞增多、红细胞沉降率加快血清心肌酶活力增高及进行性心电图变化，可发生心律失常、休克或心力衰竭 。

据科技日报报道，心肌梗死后心力衰竭的发生和发展与左心室重构紧密相关。由于心肌梗死后细胞坏死，有效的功能区域减小，心肌收缩力显著减弱或丧失，导致患者心功能不全，以致发生心力衰竭而死亡。徐标等在国际上率先采取一种新的基因——整合素连接激酶（ILK）转染到心肌梗死部位，以此促进细胞生长和心脏血管新生，恢复梗死区域的血供，研究探讨ILK是否具有调节心肌梗死后的左心室重构以及心脏功能的作用。

研究人员首先通过结扎前降支构建大鼠心梗模型，然后将表达ILK的重组腺病毒载体或者空载腺病毒注射至大鼠心脏的梗死周围区。结果显示ILK基因治疗的动物梗死周围区血管新生增强、纤维化减弱、心肌细胞凋亡减少。进一步研究发现ILK高表达具有“拯救”心室重构的作用，即心梗1周后心脏局部注射ILK病毒载体仍能部分缓解心室重构进展和改善心脏功能。

实验结果表明，ILK治疗可以改善心肌梗死后大鼠心脏重构和心功能，其治疗效果与血管新生增强、心肌细胞凋亡减少以及心肌细胞增殖水平增加有关。徐标表示，他将带领课题组继续深入研究，最终使这种基因治疗方法应用于临床心肌梗死病人的治疗，造福人类。

附：

 徐标，男，主任医师，教授。擅长冠心病介入治疗、起搏器植入、心力衰竭的抢救、高血压病、心律失常的诊治。1996年至2001年三次赴英国作高级访问学者。江苏省“135工程”医学重点人才，政府特殊津贴获得者，中华医学会南京分会心血管学会副主任委员，中华医学会南京电生理学会主任委员，兼任《中华高血压杂志》、《中华现代内科学杂志》编委，美国Circulation杂志特约审稿人。擅长冠心病介入治疗、起搏器植入、心力衰竭的抢救、高血压病、心律失常的诊治，尤其在冠脉介入及先天性心脏病介入治疗方面具有丰富的经验。主持国家自然科学基金项目研究2项，省级科研项目10余项。发表论文70余篇，SCI收录19篇，获省部级科技进步奖三项。

原文摘要：

Increased Expression of Integrin-Linked Kinase Attenuates Left Ventricular Remodeling and Improves Cardiac Function After Myocardial Infarction

Background— Left ventricular (LV) remodeling is associated with the development of heart failure after myocardial infarction. Here we investigated whether integrin-linked kinase (ILK) may regulate LV remodeling and function after myocardial infarction.

Methods and Results— Adenoviral vector expressing ILK (n=25) or empty adeno-null (n=25) was injected into rat peri-infarct myocardium after left anterior descending coronary artery ligation. ILK expression was confirmed by Western blotting and immunofluorescence. Echocardiographic and hemodynamic analyses demonstrated relatively preserved cardiac function in adeno-ILK animals. ILK treatment was associated with reduced infarct scar size, increased scar thinning ratio, and preserved LV diameter, wall thickness, cardiomyocyte size, and myofilament density. Enhanced angiogenesis and reduced fibrosis were observed in the adeno-ILK group, along with reduced apoptosis as demonstrated by terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling analysis. Moreover, increased cardiomyocyte proliferation was found in adeno-ILK animals, as measured by proliferating cell nuclear antigen, Ki-67, and phosphohistone-H3 staining. At long-term follow-up, most indices of cardiac function and hemodynamics showed no difference between adeno-ILK and control animals by 9 weeks, although LV end-systolic diameter and infarct scar size were reduced in the adeno-ILK group at this time point. Additionally, ILK overexpression was found to exert a rescue effect on remodeling when administered in a delayed fashion 1 week after coronary artery ligation.

Conclusions— ILK gene therapy improves cardiac remodeling and function in rats after myocardial infarction and is associated with increased angiogenesis, reduced apoptosis, and increased cardiomyocyte proliferation. This may represent a new approach to the treatment of postinfarct remodeling and subsequent heart failure.