低剂量STZ和L-NAME联合高脂饮食诱导的代谢综合征大鼠心肌纤维化  

Myocardial fibrosis of metabolic syndrome rats induced by low dose of STZ and L-NAME with high-fat diet

作　　者：刘晓颖[1,2] 董晖[1,3] 符永恒[1,2] 梁家亮[1,2] 王嬿[1,3] 陈达强[1,3] 杨敏[1,2] 邓春玉[1,2] 余细勇[1,2] 

机构地区：[1]广东省医学科学院 [2]广东省人民医院医学研究中心,广东广州510080 [3]广东省人民医院检验科,广东广州510080

出　　处：《广东药学院学报》2011年第2期166-169,共4页Academic Journal of Guangdong College of Pharmacy

基　　金：国家973项目(2005CB523305);广东省科技计划项目(2009B080701054);广东省中医药管理局科研基金(2010239)

摘　　要：目的建立大鼠代谢综合征(MS)模型并了解其心功能和心肌组织结构的变化特征,为其干预治疗研究提供实验平台。方法雄性SD大鼠尾静脉推注20 mg/kg STZ后高脂饲料喂养6周并予0.04%L-NAME和10%果糖混合溶液饮用,观察大鼠MS基本特征的变化。6周后处死大鼠并采用离体心脏功能实验评价心功能,HE染色及免疫荧光法分别观察心肌组织基本结构和CollagenⅠ、CollagenⅢ表达情况。结果与对照组比较,处理组大鼠在3周后血压、血浆TG、LDL及LDL/HDL均显著升高(P<0.05);6周后其空腹血糖升高,OGTT实验血糖浓度-时间曲线下AUC大于对照组(P<0.05);处理组大鼠心率、LVPP、LVDP、-dp/dtm ax及Vpm与对照组比较均明显下降,LVEDP上升(P<0.05);HE染色可见处理组大鼠左室组织肌纤维束间间隙增宽,存在连接断裂及排列紊乱现象,CollagenⅢ表达明显增加而CollagenⅠ变化不明显。结论此喂养方法诱导大鼠发生典型MS变化,并且存在明显的心肌纤维化和心功能异常,可作为研究MS心肌病变的理想动物模型。Objective To establish a rat model of metabolic syndrome and investigate the changes in cardiac function and cardiomyopaphy of the model, and to supply an experimental platform for the therapeutic study. Methods Male SD rats were fed with a high-fat diet for 6 weeks after being administered 20 mg/kg STZ through tail intravenous injection, and were given with 0.04% L-NAME solution mixed with 10% fructose through daily drinking. The change of metabolism syndrome basic characteristics was observed and recorded. Isolated heart function test was employed to determine the cardiac function of the rats. The myocardium pathological section was stained by HE and the expressions of Collagen Ⅰ and Collagen Ⅲ in myocardial tissue were detected by immunofluoreseenee. Results Blood pressure and plasma triglyceride, high-density lipoprotein and LDL/HDL levels of the treated rats were all increased significantly after 3 weeks （ P 〈 0.05 ）. The fasting plasma glucose and AUC of oral glucose tolerance test of treated group increased （ P 〈 0.05 ） after 6 weeks. The heart rate, LVPP, LVDP, - dp/dt max and Vpm of the treated rats all decreased but LVEDP increased significantly （ P 〈 0.05 ）. By staining,broken junctions and wide gaps between muscle fibers were observed in the myocardium of the treated rats, expression of Collagen m increased significantly while expression of Collagen I didnl change obviously. Conclusion Myocardial fibrosis, cardiac dysfunction and other typical changes of metabolic syndrome with high blood pressure,high glucose and lipid could be induced in treated rats with high-fat diet, which could be applied as an ideal animal model for the study of cardiac diseases in MS.

关 键 词：代谢综合征 动物模型 心肌纤维化 大鼠 

分 类 号：R589[医药卫生—内分泌]