多西环素对ApoE基因缺陷型野生小鼠主动脉夹层形成的影响  

Effect of doxycycline on aortic dissection by inhibiting matrix metalloproteinase-2 and-9 in ApoE deficient wild mice

作　　者：李明[1] West MALCOLM LI Ming;West MALCOLM(Department of Cardiovascular Surgery,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052 China;Central Laboratory,Prince Charles Hospital,Queensland University,Queensland,Brisbane4702,Australia)

机构地区：[1]郑州大学第一附属医院心血管外科,河南郑州450052 [2]澳大利亚昆士兰大学查尔斯王子医院中心实验室,澳大利亚昆士兰州布里斯班4702

出　　处：《中华实用诊断与治疗杂志》2022年第6期541-543,共3页Journal of Chinese Practical Diagnosis and Therapy

基　　金：河南省医学学术技术带头人出国培训计划项目(201201053);河南省卫生科技创新型人才工程(201004120)。

摘　　要：目的探讨多西环素抑制基质金属蛋白酶(matrix metalloproteinase,MMP)-2、MMP-9表达与ApoE基因缺陷型野生小鼠主动脉夹层形成的关系。方法成年ApoE基因缺陷型野生小鼠40只,随机分为实验组和对照组各20只,2组均给予人血管紧张素-Ⅱ1.5 mg/(kg·d)皮下注射制备主动脉夹层模型,实验组小鼠模型制备同时饮水中加入多西环素30 mg/(kg·d),对照组小鼠正常饲养。20 d后,比较2组小鼠体质量,行组织病理检查HE染色观察正常小鼠与主动脉夹层小鼠主动脉壁弹力纤维降解程度,比较2组主动脉夹层发生率;采用免疫组织化学法检测2组小鼠主动脉壁MMP-2、MMP-9表达情况。结果正常小鼠主动脉壁结构完整,弹性纤维与胶原纤维排列紧密有序;主动脉夹层小鼠主动脉壁完整性破坏,弹性纤维与胶原纤维排列杂乱无序,并伴有血液进入假腔。实验组小鼠体质量[(180.60±8.97)g]与对照组[(183.13±7.68)g]比较差异无统计学意义(t=1.113,P=0.268)。实验组小鼠主动脉夹层发生率(20%)低于对照组(75%)(χ^(2)=12.130,P=0.004),主动脉壁MMP-2、MMP-9表达水平[(1.34±0.35)、(1.98±0.33)分]均低于对照组[(2.72±0.03)、(2.65±0.12)分](t=5.974,P=0.023;t=9.134,P=0.013)。结论多西环素可有效降低ApoE基因缺陷型野生小鼠主动脉壁MMP-2、MMP-9表达,减少主动脉夹层的形成。Objective To investigate the relationships of doxycycline inhibiting the expressions of matrix metalloproteinase(MMP)-2 and MMP-9 with the formation of aortic dissection in ApoE gene deficient wild mice.Methods Forty adult ApoE deficient wild mice were randomly divided into experimental group and control group,with 20 mice in each group.Both two groups were given subcutaneous injection of human angiotensinⅡ1.5 mg/(kg·d)to establish aortic dissection models.Doxycycline 30 mg/(kg·d)was added to the drinking water in experimental group,and the mice in control group were fed normally.After 20 d,the body masses were compared between two groups.HE staining was performed for histopathological examination to observe the degradation degree of elastic fibers in the aortic wall of all mice,and the incidence rates of aortic dissection were compared between two groups.Immunohistochemical method was used to detect the expressions of MMP-2 and MMP-9 in the aortic wall in two groups.Results The structure of the aortic wall in control group was complete,and the elastic fibers and collagen fibers were arranged closely and orderly.The integrity of the aortic wall in experimental group was destroyed,the arrangement of elastic fibers and collagen fibers was disordered,and the blood entered the false cavity.There was no significant difference in the body mass between experimental group[(180.60±8.97)g]and control group[(183.13±7.68)g](t=1.113,P=0.268).The incidence rate of aortic dissection was lower in experimental group(20%)than that in control group(75%)(χ^(2)=12.130,P=0.004),and the expressions of MMP-2 and MMP-9 were lower in experimental group(1.34±0.35,1.98±0.33)than those in control group(2.72±0.03,2.65±0.12)(t=5.974,P=0.023;t=9.134,P=0.013).Conclusion Doxycycline can effectively lower the expressions of MMP-2 and MMP-9 in the aortic wall of ApoE gene deficient wild mice,and can reduce the formation of aortic dissection.

关 键 词：主动脉夹层 多西环素 小鼠 基质金属蛋白酶-2 基质金属蛋白酶-9 

分 类 号：R543.1[医药卫生—心血管疾病]