小鼠心肌纤维化模型的制备及其胶原沉积的机制  

Establishment of a mouse model of myocardial fibrosis with isoproterenol and the mechanism of collagen deposition

作　　者：邓玮[1] 陈庆伟[1] 李兴升[1] 李桂琼[1] 柯大智[1] 莫显刚[1] 

机构地区：[1]重庆医科大学附属第二医院老年病科,重庆400010

出　　处：《中国实验动物学报》2011年第2期103-106,188,共5页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金项目(编号:30970826)

摘　　要：目的建立缺血性心肌纤维化小鼠模型并探讨其胶原沉积机制。方法将BALB/c小鼠随机分为实验组和对照组,每组10只。实验组予以腹部皮下注射异丙肾上腺素50 mg/kg,每天2次,连续10 d。对照组同法注射生理盐水。对比体表心电图,45 d后处死小鼠,天狼猩红染色观察心脏Ⅰ、Ⅲ型胶原纤维含量,荧光定量PCR检测心脏基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织抑制剂-1(TIMP-1)基因表达,免疫组化染色分析心、肝、肾组织层粘连蛋白(LN)的表达。结果实验组小鼠室性心律失常增多,心率加快(P<0.05);心脏胶原沉积较多,MMP-9、TIMP-1、LN表达上调(P<0.05),肝、肾组织LN无明显改变(P>0.05)。结论异丙肾上腺素能制备缺血性心肌纤维化小鼠模型,其机制与MMP-TIMP失衡有关。Objective To establish a manipulation-easy animal model of post-ischemic myocardial fibrosis and in-vestigate the mechanism of collagen deposition.Methods Twenty BALB /c mice were randomly divided into two groups： the experimental group and control group.The mice in the experimental group were subjected to hypodermic injection with isoproterenol in a dose of 50 mg /kg.The injection was carried out twice a day for consecutive 10 days.Physiological saline was injected with the same method in the control group.The surface electrocardiogram was measured.Forty-five days after injection,collagen distribution was observed using sirius red staining.Expression levels of matrix metalloproteinase-9（MMP-9） And tissue inhibitor of metalloproteinase-1（TIMP-1） in myocardium were detected by fluorescent qRT-PCR.The expression of laminin（LN）in the heart,liver and kidney was detected by immunohistochemistry.Results The experi-mental group had increased ventricular arrhythmia and faster heart rate,and had increased levels of MMP-9,TIMP-1,LN and collagen deposition in the myocardium than those in the control group（P〈0.05）.The expression of LN in the liver and kidney showed no significant difference（P〈0.05）.Conclusions Isoproterenol-induced collagen deposition in the experiment is a reproducible,handy and credible method to establish an animal model of myocardial fibrosis.MMP-TIMP imbalance is involved in the mechanism.

关 键 词：异丙肾上腺素 心肌纤维化 小鼠 动物模型 

分 类 号：Q95-33[生物学—动物学] R542.23[医药卫生—心血管疾病]