Fgl2-shRNA基因沉默对糖尿病大鼠心功能的改善及心肌病理形态变化  

Effects of Fgl2 gene silencing on cardiac function and myocardial pathologic morphology in diabetic rats

作　　者：俞芽法 郑振中[1] 

机构地区：[1]南昌大学第一附属医院心内科,江西南昌330006 [2]江西省抚州市第一人民医院心内科,江西抚州344000

出　　处：《西安交通大学学报（医学版）》2015年第5期605-608,共4页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金资助项目(No.81260044;30960119);江西省科技支撑计划项目(No.2010BSA12000)~~

摘　　要：目的探讨慢病毒介导的纤维介素(fgl2)基因沉默对糖尿病(DM)大鼠心功能的影响及其在心肌组织中的表达。方法雄性SD大鼠腹腔注射STZ建立DM模型,随机分组为fgl2基因沉默组、GFP空载体组、DM模型组(DM组),基因沉默及GFP空载体组分别尾静脉注射慢病毒载体1×109 IU,DM组注射生理盐水;另设对照组(各组8只)。14周后超声检测左室射血分数(LVEF)、左室短轴缩短率(即缩短分数,FS)、心率(HR)等,心肌组织进行HE染色观察病理形态及免疫组化染色检测fgl2表达。结果 DM组大鼠LVEF、FS降低,HR减少;HE染色示心肌纤维排列紊乱、纵横纹模糊、部分区域变性等;免疫组化fgl2染色示微血管内及周围大量棕黄色絮状染色。fgl2基因沉默组LVEF、FS、HR较DM组提高,差异有统计学意义(P<0.05);病理形态学表现为心肌纤维排列稍紊乱;免疫组化结果显示微血管内少量棕黄色絮状染色,较DM组明显减少,灰度值差异有统计学意义(P<0.05)。结论 Fgl2基因沉默下调DM大鼠心肌fgl2表达,改善病理形态,抑制心室重构,保护心脏功能。Objective To investigate the effects of fibrinogen-like protein2（fgl2）gene silencing mediated by lentivirus on cardiac function in diabetes mellitus（DM）rats and its expression in myocardial tissue.MethodsAdult male Sprague-Dawley rats were randomly divided into control group and model group.Streptozotocin（STZ）was injected intraperitoneally in model group.Diabetes rats were randomly divided into1fgl2-LV RNAi group（n=8）fgl2 lentivirus vector 1×109 IU/n,injected by tail vein rapidly,2 GFP-lentivirus sh-RNAi group（n=8）,GFP-lentivirus sh-RNAi 1×109 IU/n injected rapidly by tail vein;3 diabetes group,saline solution injected by tail vein.Cardiac functions of the rats including left ventricular ejection fraction（LVEF）,left ventricular short axis reduced rate（FS）,and heart rate（HR）were tested by ultrasonic method after 14 weeks.Myocardial tissue was fixed by formaldehyde for pathological slices.The pathological morphology was observed by HE staining and the expression of fgl2 was detected by immunohistochemical method.Results The cardiac functions of DM rats were impaired.LVEF,FS and HR were reduced;the arrangement of myocardial fibers was disordered;myocardial fibers were blurry with degeneration in some regions.A lot of brownish yellow flocculent staining of fgl2 could be observed in and around myocardial microvessels in diabetic group.LVEF,FS and HR increased significantly in fgl2 shRNAi group compared with DM group（P〈0.05）.The arrangement of myocardial fibers was disorderly,and a small amount of brownish yellow flocculent dyeing within microvessels was shown by immunohistochemical method.The gray value decreased significantly compared with that in DM group（P〈0.05）.Conclusion Fgl2 gene silencing may downregulate the expression fgl2 in the myocardium of DM rats,improve pathologic morphology,and inhibit ventricular remodeling,thus protecting heart function.

关 键 词：纤维介素(fgl2) 糖尿病 糖尿病心肌病 基因沉默 心室重构 

分 类 号：R587.1[医药卫生—内分泌]