基质金属蛋白酶及其抑制物在容量过负荷致慢性心力衰竭大鼠血浆及心肌组织中的变化及意义  

Changes and Significance of Matrix Metalloproteinase and Its Tissue Inhibitor in Plasma and Cardiac Muscle of Rats with Chronic Cardiac Failure Induced by Volume Overload

作　　者：张超英[1] 李晓惠[1] 伏瑾[2] 崔小岱[2] 

机构地区：[1]首都儿科研究所附属儿童医院内科,北京100020 [2]首都儿科研究所附属儿童医院临床中心实验室,北京100020

出　　处：《实用儿科临床杂志》2011年第13期992-994,共3页Journal of Applied Clinical Pediatrics

基　　金：国家自然科学基金(30872787);北京市优秀人才培养资助项目(20081D0303200107);北京市卫生局青年科学研究资助项目(QN2007-08)

摘　　要：目的观察容量过负荷致慢性心力衰竭大鼠血浆及心肌组织基质金属蛋白酶-8(MMP-8)及其抑制物-1(TIMP-1)的表达变化,探讨其在慢性心力衰竭发病中的病理生理作用。方法雄性SD大鼠17只,随机分为分流组(n=9)和对照组(n=8)。分流组通过腹主动脉下腔静脉穿刺术建立容量过负荷致慢性充血性心力衰竭动物模型,对照组大鼠除不做穿刺外,余操作过程同分流组。分别测定2组大鼠心功能及血流动力学指标,检测血浆MMP-8及TIMP-1水平,实时荧光定量PCR测定大鼠左心室、右心室MMP-8 mRNA、TIMP-1 mRNA的表达。结果术后8周,分流组大鼠左心室收缩压、左心室舒张压、左心室内压差、左心室内压最大上升速率及最大下降速率较对照组明显降低(Pa<0.05,0.01);左心室舒张末压较对照组明显升高(P<0.05)。分流组大鼠血浆MMP-8、TIMP-1水平均较对照组明显升高(Pa<0.05)。与对照组相比,分流组大鼠左心室心肌组织MMP-8 mRNA及左、右心室心肌组织TIMP-1 mRNA水平均有升高趋势,右心室MMP-8 mRNA水平有下降趋势,但2组比较差异均无统计学意义(Pa>0.05);左心室和右心室心肌组织中MMP-8/TIMP-1明显降低,右心室较左心室下降更明显。结论 MMP-8与TIMP-1通过影响胶原代谢,参与容量过负荷致慢性充血性心力衰竭的病理生理过程。Objective To observe the changes of matrix metalloproteinase-8（MMP-8） and its tissue inhibitors of metallopreteinase-1（TIMP-1） in plasma and cardiac muscle of rats with chronic cardiac failure induced by volume overload,and to explore those roles in phy-siology of chronic cardiac failure.Methods Seventeen male SD rats were randomly divided into 2 groups as follows：9 shunt rat models were established by abdominal aorta and inferior vena cava shunt operation and 8 rats after sham operation served as controls.Hemodynamic and echocardiographic measurements were obtained 8 weeks after surgery.Meanwhile,MMP-8 and TIMP-1 concentrations in plasma were eva-luated.MMP-8 mRNA and TIMP-1 mRNA expressions were detected by using real time reverse transcription polymerase chain reaction method in cardiac muscle.Results Left ventricular systolic pressure,difference of left ventricular pressure,left ventricular diastolic,left ventricular peak rate of contraction,left ventricular peak rate of relaxation were significantly reduced in the shunt group compared with those in control group（Pa0.05,0.01）.Compared with control group,left ventricular end diastolic pressure were significantly increased in shunt group（P0.05）.Compared with control group,the plasma levels of MMP-8 and TIMP-1 mRNA increased significantly in shunt group（Pa0.05）.The expressions of MMP-8 mRNA and TIMP-1 mRNA in cardiac muscle were similar between the 2 groups（Pa0.05）.The ratio of MMP-8/TIMP-1 significantly decreased in shunt group as compared with that in control group,which was more significant in right ventricular than that in left ventricular.Conclusion MMP-8 and TIMP-1 are involved in ventricular remodeling in rats with chronic cardiac failure resulting from volume overload.

关 键 词：容量负荷 基质金属蛋白酶 基质金属蛋白酶组织抑制剂 心室重建 

分 类 号：R541.6[医药卫生—心血管疾病]