单纯收缩期高血压大鼠模型建立及基质金属蛋白酶-9在其形成中的作用  

Making of model of isolated systolic hypertension rats and its mechanism

作　　者：吴雅利[1,2,3] 朱光照 邬甦[1,2,3] 陈慰云[5] 雷梦觉[1,2,3] 

机构地区：[1]江西省人民医院干部心内二科 [2]江西省心血管病研究所 [3]江西省老年医学研究所,江西南昌330006 [4]新余市人民医院 [5]南昌大学医学院基础部

出　　处：《中国老年学杂志》2013年第8期1848-1851,共4页Chinese Journal of Gerontology

基　　金：江西省卫生厅重大攻关课题(20074002)

摘　　要：目的探讨单纯收缩期高血压(ISH)模型的建立及基质金属蛋白酶(MMP)-9在其形成中的作用。方法选用8周龄Wistar雄性大鼠20只作为研究对象,随机分成模型组(n=10)和对照组(n=10)。应用华法林和维生素K诱导动脉中层钙化,8 w后右侧颈动脉插管进行有创血压和心室内压力的检测。以及取材主动脉,Von Kossa染色分析动脉钙化程度;采用原子吸收光谱法测定血管组织中钙含量。采用弹性纤维染色法观察主动脉组织中弹性纤维形状;应用免疫组织化学和Western印迹检测主动脉组织中MMP-9的表达水平。结果模型组大鼠血压与对照组相比明显增高(P<0.01);而各组间平均心室内压无明显变化。模型组大鼠血压变化的同时伴有动脉形态结构的改变,主动脉和颈动脉中层钙化明显,模型组动脉钙含量明显高于对照组(P<0.01)。弹力纤维断裂变直,失去波浪形状。Western印迹分析模型组MMP-9蛋白表达较对照组明显升高。结论利用法华林和维生素K诱导的ISH大鼠是可重复好,便捷,以及与人体衰老相似较为理想的模型。MMP-9酶表达明显增多可促使大动脉中层弹力蛋白降解和钙在弹力纤维薄层的沉积,从而在ISH形成中发挥重要作用。Objective To investigate whether matrix metalloproteinase （MMP）-9 could interfere the formation of isolated systolic hypertension （ISH） so as to provide a new model of ISH. Methods 8 weeks age-matched male Wistar tats were selected to study, all 20 the rats were randomly divided into the intervention group （n = 10）, and control group （n = 10）. To induce large artery calcification, rats were treated with warfarin and vitamin K1 for 8 weeks, to inhibit the maturation of matrix Gla. 8 weeks later, blood pressure and left ventric-ular pressure were measured by right carotid arterial cannulation, and the segments from each aorta was processed for histological analysis by Calcium analysis/Von Kossa method. Aortic calcium contents were calculated in each group with atom-spectrum. Elastic/collagen ratio was measured according to different coloration methods. MMP-9 was explored by immunohistochemistry and Western-blot. Results The blood pressures in the intervention group were higher than those of control group （P 〈 0. 01 ）. There was no significant difference in mean left ven-tricular pressure in the study group. The blood pressure of ISH animal changed with morphological aspect of each aorta, which was associated with extensive arterial medial elastocalcinosis, and the elastic lamellae was flatten, accompanied loss of the natural waviness. Western-blot a- nalysis showed that protein synthesis of MMP-9 in the intervention group was increased obviously as compared with that of the control group. Conclusions Chronic treatment with vitamin K represents a new model of ISH with several characteristics of the human disease. The pres-ence of MMP-9 is required for elastin degeneration and calcification in the aortic elastic fibers, which plays a role in the formation of ISH.

关 键 词：单纯收缩期高血压 动脉钙化 基质金属蛋白酶 

分 类 号：R541.4[医药卫生—心血管疾病]