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目的:通过galectin-3(gal-3)抑制剂——改良的柑橘果胶(modified citrus pectin,MCP)治疗心肌梗死后心功能不全家兔,探讨MCP对缺血性心功能不全的治疗作用。方法:(1)30只家兔随机分为假手术组、心功能不全组、MCP组;(2)结扎冠状动脉前降支制作家兔心肌梗死后心功能不全模型,心功能不全模型制作成功后,MCP组予75mg/ml MCP(2ml·kg-1·d-1)、假手术组及心功能不全组予0.9%氯化钠溶液(2ml·kg-1·d-1)各灌胃4周;(3)心脏超声仪、ELISA法分别检测家兔术前及术后2、4、6周心功能及血清gal-3表达情况;(4)RT-PCR和WesternBlot分析心肌梗死边缘区gal-3、胶原蛋白Ⅰ、胶原蛋白ⅢmRNA和蛋白表达水平,并计算胶原蛋白Ⅰ/Ⅲ比值;(5)给药4周后取各组心肌梗死边缘区组织,用Masson法胶原染色分析心肌梗死边缘区纤维化。结果:(1)给药2周、4周后MCP组心功能较心功能不全组明显好转(P<0.01);(2)给药2周、4周后心功能不全组血清gal-3浓度远远高于MCP组(P<0.05);(3)给药4周后心功能不全组梗死边缘区gal-3、胶原蛋白Ⅰ、胶原蛋白Ⅲ的mRNA表达较MCP组均明显增高(P<0.01);(4)光学显微镜下心功能不全组可见心肌细胞排列紊乱,部分心肌细胞坏死、水肿、肥大,心肌纤维增粗。小血管壁增厚并可见周围有大量蓝绿色胶原纤维增生并包绕分割心肌细胞,心肌间质纤维增生、胶原大量沉积并伴有炎性细胞浸润;(5)心功能不全组中梗死边缘区域心肌组织gal-3、胶原蛋白Ⅰ、胶原蛋白Ⅲ蛋白表达明显高于MCP组和假手术组。结论:在心功能不全家兔中,gal-3表达的增加与心脏功能不全、纤维化、心肌胶原蛋白大量沉积有关,但是通过MCP可以阻止gal-3的表达,改善心肌梗死边缘区域的纤维化程度。gal-3在心室重构和其引起的功能障碍中起到关键的作用,gal-3或许可作为治疗心力衰竭新的靶点。
OBJECTIVE: To investigate the therapeutic effect of MCP on ischemic cardiac dysfunction in rabbits with heart failure after myocardial infarction by using galectin-3 (gal-3) inhibitor-modified citrus pectin (MCP) Methods: (1) Thirty rabbits were randomly divided into sham-operated group, cardiac dysfunction group and MCP group. (2) Rabbits with myocardial infarction after ligation of the anterior descending coronary artery were sacrificed to establish a model of cardiac insufficiency After treatment with MCP (2ml · kg-1 · d-1) for 75mg / ml, 0.9% sodium chloride solution (2ml · kg-1 · d-1) 4 weeks; (3) Heart function and serum gal-3 expression in rabbit preoperatively and at 2, 4, 6 and 6 weeks after myocardial infarction were detected by echocardiography and ELISA; (4) (5) After 4 weeks of administration, the marginal zone tissue of each group was taken and the myocardial infarction was analyzed by Masson’s method. The results showed that the collagen Ⅰ, Ⅲ, Marginal zone fibrosis. Results: (1) After 2 weeks and 4 weeks of administration, the cardiac function of the MCP group was significantly improved compared with the cardiac insufficiency group (P <0.01); (2) Serum gal-3 levels in the patients with cardiac insufficiency (P <0.05). (3) The mRNA expression of gal-3, collagen Ⅰ and collagen Ⅲ in the marginal zone of myocardial infarction group were significantly higher than those in MCP group after 4 weeks of administration (P <0.01); 4) Under the optical microscope, cardiac dysfunction group showed disorganized cardiomyocytes, some myocardial cell necrosis, edema, hypertrophy, myocardial fiber thickening. Small vascular wall thickening and visible around a large number of blue-green collagen fibrosis and around the division of myocardial cells, myocardial interstitial fibrosis, collagen deposition and a large number of inflammatory cells infiltration; (5) infarction in patients with cardiac insufficiency Myocardial tissue gal-3, collagen Ⅰ, collagen Ⅲ protein expression was significantly higher than the MCP group and sham operation group. CONCLUSIONS: The increased expression of gal-3 is associated with cardiac dysfunction, fibrosis, and heavy deposits of myocardial collagen in heart failure rabbits. However, MCP inhibits the expression of gal-3 and improves the fibrosis in the marginal area of myocardial infarction . Gal-3 plays a pivotal role in ventricular remodeling and the dysfunction it causes, and gal-3 may serve as a new target for the treatment of heart failure.