氨甲酰化促红细胞生成素逆转慢性心力衰竭大鼠心肌重塑的作用  

Effect of Carbamylated Erythropoietin reverses myocardial remodeling in rats with chronic heart failure

作　　者：谈丽丽[1] 王志禄[2] 王锋[1] 崔丽君[1] 张丽[1] 许哲通[3] 贾军正[1] 李万玲[1] 郭文芬[1] 

机构地区：[1]兰州大学第一临床医学院,兰州730000 [2]兰州大学第一医院心内科 [3]保定市第二人民医院心内科

出　　处：《临床心血管病杂志》2011年第4期257-260,共4页Journal of Clinical Cardiology

基　　金：甘肃省新药临床前研究重点实验室开放基金(No:GSKFKT-0707)

摘　　要：目的:观察血清基质金属蛋白酶-2(Matrix metalloproteinase-2,MMP-2)及其组织抑制因子(Tissueinhibitor of metalloproteinase-1,TIMP-1)水平与心肌胶原容积指数(CVF)的变化,探讨氨甲酰化促红细胞生成素(CEPO)对慢性心力衰竭(CHF)心肌重塑的作用及其机制。方法:从80只Wistar雄性大鼠中随机选取10只作为对照组,其余腹腔注射异丙肾上腺素建立CHF模型。5周后将造模成功的大鼠再随机分为2组:CHF组(n=18);CEPO组(n=18),腹腔注射CEPO 50μg/kg,2次/周,连续4周。CHF组和对照组同期腹腔注射等量0.9%氯化钠溶液。4周后检测3组大鼠血流动力学指标、左心室重量指数(LVMI)和血清MMP-2及TIMP-1水平与CVF的变化。结果:与对照组相比,CHF组左室收缩压(LVSP)、左室内压上升/下降最大速率(±dp/dtmax)绝对值均显著降低(P<0.01),左室舒张压(LVDP)、左室舒张末压(LVEDP)升高(P<0.01),血清MMP-2升高(P<0.01)而TIMP-1降低(P<0.01),LVMI及CVF升高(P<0.01);与CHF组相比,CEPO组大鼠血流动力学各指标变化均有显著差异(P<0.01),血清MMP-2水平降低(P<0.01)、TIMP-1水平升高(P<0.01),LVMI及CVF降低(P<0.01)。结论:CEPO有明确的抗心力衰竭作用,通过调节MMP-2和TIMP-1的表达,降解细胞外基质胶原含量,逆转心肌重塑,从而改善心脏功能。Objective：In order to explore carbamylated erythropoietin（CEPO）＇s effect in chronic heart failure（CHF）area,besides many studies have already shown CEPO has clearly cardioprotective effect in other areas.Levels of serum Matrix Metalloproteinase-2（MMP-2）,Tissue Inhibitor of Metalloproteinase-1（TIMP-1） and Volume Fraction of Collagen（CVF） were assessed to reflect whether CEPO has cardioprotective effect in rats with CHF and its possible mechanisms.Method：10 of 80 Wistar rats have been randomly selected as control group,other 70 rats were injected with isoprenaline intraperitonealy to establish CHF models.After nine weeks,when CHF models were established successfully,CHF rats were divided into two groups,CHF group（n=18） and CEPO group（n=18）.CEPO group were injected intraperitonealy CEPO 50 μg/kg,twice a week,while CHF and control group were received the same volume of normal saline at the same time.After four weeks,hemodynamic parameter,Left Ventricular Mass Index（LVMI）,the level of serum MMP-2,TIMP-1 and CVF were evaluated respectively.Result：Compared with control group,Left Ventricular Systolic Pressure（LVSP）,maximal rate of rise/decline of left ventricular pressure（±dp/dtmax）（P0.01 for each） were significantly decreased,on the other hand,Left ventricular diastolic pressure（LVDP） and Left Ventricular End Diastolic Pressure（LVEDP） were significantly increased（P0.01）,the level of serum MMP-2,LVMI and CVF were increased too,but TIMP-1 was decreased（P0.01） in CHF group;Secondly,compared with CHF group,CEPO group have higher LVSP,±dp/dtmax and level of serum TIMP-1（P0.01）,lower LVDP,LVEDP,level of serum MMP-2,LVMI and CVF（P0.01）.Conclusion：CEPO could reverse myocardial remodeling,improve cardiac function in rats with CHF through regulate the expression of MMP-2,TIMP 1 and degredate the volume of collagen.

关 键 词：慢性心力衰竭 氨甲酰化促红细胞生成素 心肌重塑 基质金属蛋白酶-2 基质金属蛋白酶组织抑制剂-1 

分 类 号：R541.6[医药卫生—心血管疾病]