基质金属蛋白酶与血管紧张素Ⅱ在病毒性心肌炎小鼠心肌胶原重构中的作用  

THE ROLES OF MATRIX METALLOPROTEINASES AND ANGIOTENSIN Ⅱ IN MYOCARDIAL COLLAGEN REMODELING IN MICE WITH COXSACKIEVIRUS MYOCARDITIS

作　　者：刘唐威[1] 覃远汉[2] 伍伟锋[1] 庞玉生[2] 胡鹏[2] 林伟雄[1] 李佳荃[1] 

机构地区：[1]广西医科大学第一附属医院心内科,南宁530021 [2]广西医科大学第一附属医院儿科,南宁530021

出　　处：《广西医科大学学报》2006年第5期695-698,共4页Journal of Guangxi Medical University

基　　金：广西科学基金资助项目(桂科基0448048)

摘　　要：目的：探讨病毒性心肌炎（VM）小鼠心肌基质金属蛋白酶-3（MMP-3）及金属蛋白酶组织抑制因子-1（TIMP—1）与血管紧张素Ⅱ（AngⅡ）的关系及其在心肌胶原重构中的作用．方法：80只鼠龄4—6周Balb／c纯种雄性小鼠随机分为对照组（n=20）、感染组（n=60）。感染组小鼠腹腔接种0．1ml的Coxsakievirus B3（CVB3）建立VM模型，对照组腹腔注射不含CVB3的0．1ml Hep-2细胞冻溶液。感染组于注射CVB3后第7、14、28、42天，对照组于第42天分别处死小鼠．氯氨T法测定心肌胶原含量；免疫组化法检测心肌Ⅰ／Ⅲ型胶原比值；放射免疫法检测心肌AngⅡ含量；逆转录-聚合酶链反应法（RT-PCR）检测心肌MMP-3和T1MP—1 mRNA的表达．结果：感染组小鼠心肌MMP-3mRNA表达上调，TIMP—1mRNA表达下调，以第14、28天表达最显着；TIMP-1于第42天表达上调。第28天和第42天感染组小鼠心肌AngⅡ含量、胶原含量和Ⅰ／Ⅲ型胶原比值显着增高。心肌AngⅡ含量与心肌胶原含量、心肌MMP-3的表达呈正相关（r分别为0．549，0．624，P〈0．05），与心肌TIMP-1的表达呈负相关（r=-0．554，P〈0．05）。结论：VM小鼠心肌MMP-3、TIMP-1与心肌AngⅡ密切相关，可能在心肌胶原重构中起重要作用。Objective：Abstract Objective： To explore the relationship of myocardial matrix metalloproteinase-3 （MMP-3） and tissue inhibitor of metalloproteinase-1 （TIMP-1） with angiotensin Ⅱ （Ang Ⅱ ） and its roles in myocardial collagen remodeling in mice with Coxsackievirus myocarditis （VM）. Methods： Eighty four to six-week-old male Balb/c mice were divided into control group（ n =20） and infected group（ n =60） randomly. Mice in the infected group were inoculated intrapritoneally with 0. 1 ml of Coxsackie virus B3 （CVB3 Nancy strain）. Control mice were inoculated intrapritoneally with 0.1 ml of Hep-2 cell refrigerant solution excluding virus. The infected mice were sacrificed on day 7, 14, 28 and 42 respectively and the control mice were killed on day 42 after inoculation. Myocardial collagen contents were measured by determination of hydroxyproline quantification, the ratio of collagen Ⅰ /Ⅲ was measured by immunohistochemistry, myocardial Ang Ⅱ contents were measured by radioimmunoassay, and the mRNA expressions of MMP-3 and TIMP-1 were detected by reverse transcription-polymerase chain reaction （RT-PCR）. Result： In the virus-infected mice, the mRNA expression of MMP-3 was upregulated and the mRNA expression of TIMP-1 was downregulated significantly on day 14 and day 28, the mRNA expression of TIMP-1 was upregulated remarkably on day 42 compared with those in controls, and myocardial Ang Ⅱ contents, myocardial collagen contents and the ratio of collagen Ⅰ /Ⅲ were increased significantly on day 28 and day 42. Myocardial Ang Ⅱ contents positively correlated with the mRNA expression of MMP-3 and myocardial collagen contents （r=0. 549,0. 624, P〈0.05）, and they negatively correlated with the mRNA expression of TIMP-1 （r=-0. 554, P〈0. 05）. Conclusion： The changes of myocardial MMP-3 and TIMP-1 were associated with myocardial Ang Ⅱ contents of VM, and may contributes to myocardial collagen remodeling in myocarditis mice.

关 键 词：基质金属蛋白酶 血管紧张素Ⅱ 病毒性心肌炎 心肌胶原重构 

分 类 号：R542.21[医药卫生—心血管疾病]