摘要
目的通过半乳糖凝聚素3(Gal-3)特异性竞争拮抗剂——改良柑橘果胶(MCP)抑制Gal-3途径,探讨Gal-3在心功能不全心室重构中的作用。方法将30只家兔随机分为假手术组、心功能不全组、MCP组。结扎冠状动脉前降支,制作心肌梗死后心功能不全模型。模型制作成功后,MCP组用生理盐水配置75 g/L MCP,以2 m L/(kg·d)灌胃4周;假手术组及心功能不全组给予生理盐水2 m L/(kg·d)灌胃4周。术前及术后2、4、6周,用心脏超声仪测定各组家兔心功能,ELISA检测血清Gal-3、脑钠肽(BNP)水平。实时荧光定量PCR检测心肌组织Gal-3、胶原蛋白Ⅰ、ⅢmRNA的表达,计算Ⅰ/Ⅲ比值。术后6周,Masson染色观察心肌梗死区域组织病理学情况,Western blot检测Gal-3、胶原蛋白Ⅰ、Ⅲ的蛋白表达。结果给药4周后MCP组心功能较心功能不全组明显好转(P<0.01)。心功能不全组血清Gal-3高于假手术组(P<0.05),MCP组血清Gal-3较心功能不全组明显下降(P<0.05)。相关性分析显示,心功能不全组家兔心功能左心室射血分数与血清Gal-3呈负相关性(r=-0.841,P=0.009),左心室舒张末期内径与血清Gal-3呈正相关(r=0.905,P=0.002)。与心功能不全组相比,MCP组Gal-3、胶原蛋白Ⅰ、ⅢmRNA表达明显减低(P<0.05)。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,胶原大量沉积并伴有炎性细胞浸润;MCP组可见心肌纤维增粗,排列稍整齐。心功能不全组梗死区域心肌组织Gal-3、胶原蛋白Ⅰ、Ⅲ蛋白表达明显高于MCP组和假手术组;相关性分析显示,心功能不全组梗死区域Gal-3与胶原蛋白Ⅲ呈正相关(r=0.793,P=0.019)。结论 Gal-3在心力衰竭心室重构和心肌纤维化进展中起到关键的作用。
Aim To investigate the role of galectin-3 （Gal-3） in ventricular remodeling of heart insufficiency, via the pathway of Gal-3 specific competitive antagonist--modified citrus pectin （MCP） inhibiting Gal-3. Methods 30 rabbits were randomly divided into sham operation group, cardiac insufficiency group and MCP group. A model of cardiac dysfunction after myocardial infarction was made by ligating the anterior descending branch of coronary artery. After the model was successfully made, MCP group was treated with 75 g/L MCP allocated with normal saline, and intragastric ad- ministration for 4 weeks with 2 mL/（ kg ·d）, and sham operation group and cardiac insufficiency group received the intra- gastric administration of 2 mL/（kg · d） normal saline for 4 weeks. Before operation and 2, 4, 6 weeks after operation, cardiac function was measured by cardiac ultrasound, and serum levels of Gal-3 and brain natriuretic peptide （BNP） were detected by ELISA. The mRNA expressions of Gal-3, collagen I and IU in myocardial tissue were detected by real-time quantitative PCR, and the ratio of Ⅰ /Ⅲ was calculated. 6 weeks after operation, Masson staining was used to observe the histopathology of myocardial infarction region, and the protein expressions of Gal-3, collagen I and m were detected by Western blot. Results After 4 weeks of administration, the heart function of the MCP group was significantly improved compared with the cardiac insufficiency group （P〈0.01）. The serum Gal-3 in cardiac insufficiency group was higher than that in sham operation group （P〈0.05） , and serum Gal-3 in MCP group was significantly lower than that in cardiac insuffi- ciency group （P〈0.05）. Correlation analysis showed that left ventricular ejection fraction was negatively correlated with serum Gal-3 （r=-0.841, P=0.009）, and left ventricular end-diastolic diameter was positively correlated with serum Gal-3 （r= 0.905, P=0.002）, in cardiac insufficiency group. Compared with cardiac insufficiency group, the mRNA expression of Gal-3, collagen I and Ⅲ in MCP group was significantly decreased （P〈0.05）. Under optical microscope, cardiac in- sufficiency group showed myocardial cell disorder, part of myocardial cell necrosis, edema, acollagen deposition and in- flammatory cell infiltration; MCP group showed myocardial fiber thickening, arranging in a slightly tidy order. Protein ex- pressions of Gal-3, collagen I and Ⅲ in the infarcted myocardium of cardiac insufficiency group were significantly higher than those in MCP group and sham operation group. Correlation analysis showed that Gal-3 in infarction region was posi- tively correlated with collagen Ⅲ in cardiac insufficiency group （r = 0.793, P = 0.019）. Conclusion Gal-3 plays a key role in the progressions of ventricular remodeling and myocardial fibrosis in heart failure.
作者
邓文浩
李树仁
张跃华
郝潇
李沙
马玉龙
DENG Wen-Hao LIShu-Ren ZHANG Yue-Hua HAO Xiao LI Sha MA Yu-Long(Graduate College, Hebei Medical University, Shijiazhuang, Hebei 050011, China Department of Cardiology, Hebei People＇s Hospital, Shijiazhuang, Hebei 050051, China)
出处
《中国动脉硬化杂志》
CAS
北大核心
2017年第10期1008-1014,共7页
Chinese Journal of Arteriosclerosis
