Galectin-3拮抗剂——MCP对缺血性心功能不全的作用  

Effect of Galectin-3 antagonist-MCP on ischemic heart failure

作　　者：邓文浩[1] 李树仁[1] 张跃华[1] 周蕾[2] 郝潇[1] 马玉龙[1] 李沙[1] 

机构地区：[1]河北医科大学附属河北省人民医院心脏一科,石家庄050051 [2]河北北方学院附属石家庄市中医院

出　　处：《临床心血管病杂志》2017年第6期554-559,共6页Journal of Clinical Cardiology

摘　　要：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 explore the effect of modified citrus pectin（MCP）on heart failure post myocardial infarction in rabbits.Method：Thirty rabbits were randomly divided into sham operation group,heart faliure group and MCP group.Rabbits of the MCP groups were treated with MCP split normal saline solution 2ml/kg/d via intragastric administration（75 mg/ml）for 4 weeks.The sham operation group and the cardiac dysfunction group were given normal saline（2 ml/kg/d）for 4 weeks.The cardiac function and the expression of galectin-3 were measured by radioimmunoassay and ELISA at 2weeks,4weeks and 6weeks after operation.PCR and WesternBlot were used to analyze the expression of galectin-3,CollagenⅠ,CollagenⅢ mRNA and protein in the marginal zone of myocardial infarction.The ratio of collagenⅠ/Ⅲ was calculated.Fibrosis in fringe of myocardial infarction was analyzed by masson collagen staining.Result：The cardiac function of MCP group were significantly improved（P〈0.01）at 2weeks and 4weeks.The concentration of galectin-3in heart failure group was significantly higher than that in MCP group（P〈0.05）.The mRNA expressions of galectin-3,collagenⅠand collagenⅢ were significantly higher in the endge of infarction of the heart failure group than those in the MCP group（P〈0.01）.The expression of galectin-3,CollagenⅠand CollagenⅢin the infarcted area of heart faliure group was significantly higher than that of MCP group and sham operation group.Conclusion：The increased expression of galectin-3is associated with cardiac insufficiency,fibrosis,and cardiac collagen deposition in rabbits with heart failure,which could be inhibited by MCP.

关 键 词：半乳糖凝聚素-3 改良的柑橘果胶 心肌纤维化 心室重构 

分 类 号：R541.4[医药卫生—心血管疾病]