Galectin-3拮抗劑——MCP對缺血性心功能不全的作用
發(fā)布時(shí)間:2018-05-07 07:19
本文選題:半乳糖凝聚素- + 改良的柑橘果膠 ; 參考:《臨床心血管病雜志》2017年06期
【摘要】:目的:通過galectin-3(gal-3)抑制劑——改良的柑橘果膠(modified citrus pectin,MCP)治療心肌梗死后心功能不全家兔,探討MCP對缺血性心功能不全的治療作用。方法:(1)30只家兔隨機(jī)分為假手術(shù)組、心功能不全組、MCP組;(2)結(jié)扎冠狀動(dòng)脈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組予75mg/ml MCP(2ml·kg-1·d-1)、假手術(shù)組及心功能不全組予0.9%氯化鈉溶液(2ml·kg-1·d-1)各灌胃4周;(3)心臟超聲儀、ELISA法分別檢測家兔術(shù)前及術(shù)后2、4、6周心功能及血清gal-3表達(dá)情況;(4)RT-PCR和WesternBlot分析心肌梗死邊緣區(qū)gal-3、膠原蛋白Ⅰ、膠原蛋白ⅢmRNA和蛋白表達(dá)水平,并計(jì)算膠原蛋白Ⅰ/Ⅲ比值;(5)給藥4周后取各組心肌梗死邊緣區(qū)組織,用Masson法膠原染色分析心肌梗死邊緣區(qū)纖維化。結(jié)果:(1)給藥2周、4周后MCP組心功能較心功能不全組明顯好轉(zhuǎn)(P0.01);(2)給藥2周、4周后心功能不全組血清gal-3濃度遠(yuǎn)遠(yuǎn)高于MCP組(P0.05);(3)給藥4周后心功能不全組梗死邊緣區(qū)gal-3、膠原蛋白Ⅰ、膠原蛋白Ⅲ的mRNA表達(dá)較MCP組均明顯增高(P0.01);(4)光學(xué)顯微鏡下心功能不全組可見心肌細(xì)胞排列紊亂,部分心肌細(xì)胞壞死、水腫、肥大,心肌纖維增粗。小血管壁增厚并可見周圍有大量藍(lán)綠色膠原纖維增生并包繞分割心肌細(xì)胞,心肌間質(zhì)纖維增生、膠原大量沉積并伴有炎性細(xì)胞浸潤;(5)心功能不全組中梗死邊緣區(qū)域心肌組織gal-3、膠原蛋白Ⅰ、膠原蛋白Ⅲ蛋白表達(dá)明顯高于MCP組和假手術(shù)組。結(jié)論:在心功能不全家兔中,gal-3表達(dá)的增加與心臟功能不全、纖維化、心肌膠原蛋白大量沉積有關(guān),但是通過MCP可以阻止gal-3的表達(dá),改善心肌梗死邊緣區(qū)域的纖維化程度。gal-3在心室重構(gòu)和其引起的功能障礙中起到關(guān)鍵的作用,gal-3或許可作為治療心力衰竭新的靶點(diǎn)。
[Abstract]:Aim: to study the therapeutic effect of MCP on ischemic cardiac dysfunction in rabbits with myocardial infarction by modified citrus pectinus (citrus), a galectin-3gal-3 inhibitor. Methods Thirty rabbits were randomly divided into sham-operation group (MCP group) and MCP group (2) ligation of anterior descending branch of coronary artery to make the model of cardiac insufficiency after myocardial infarction in rabbits. After successful cardiac insufficiency model, 75mg/ml MCP(2ml kg-1 d-1 was given to MCP group, 0.9% sodium chloride solution was given to 2 ml kg-1 d-1 in sham operation group and cardiac insufficiency group was given 0.9% sodium chloride solution for 4 weeks. The cardiac function and serum gal-3 were measured by Elisa before operation and 2 weeks after operation by using hypersonic enzyme linked immunosorbent assay (Elisa). RT-PCR and WesternBlot were used to analyze gal-3, collagen 鈪,
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