小鼠主动脉弓缩窄模型的建立及评价  

Establishment and Assessment of a Mouse Model of Aortic Arch Constriction

作　　者：李晓梅[1] 马依彤[1] 杨毅宁[1] 高晓明 刘芬[1] 韩伟[1] 张健发[1] 

机构地区：[1]新疆医科大学第一附属医院心脏中心,乌鲁木齐830054 [2]Baker心脏研究所实验心脏病学研究室,澳大利亚Melbourne 6492

出　　处：《中国比较医学杂志》2008年第11期24-29,86,共7页Chinese Journal of Comparative Medicine

基　　金：新疆维吾尔自治区高校科研计划创新研究群体基金(XJEDU2005G03)

摘　　要：目的通过显微外科技术建立小鼠主动脉弓缩窄压力超负荷模型,探讨心脏形态及功能变化的规律。方法135只雄性昆明小鼠随机分为主动脉弓缩窄组75只和假手术组60只。在术前、术后1周、4周、6周、8周1、2周进行高频心脏超声、血流动力学、心脏病理学检测,并对器官称重,对死亡原因进行分析。结果(1)主动脉弓缩窄手术成功率为88%;(2)与假手术组比较,术后4周,缩窄组小鼠出现左室向心性肥厚,左心室收缩期、舒张期后壁厚度(Pwsth;Pwdth)、左心室重量指数(LVMI)显著增加(P<0.05),术后6、8、12周上述指标呈轻度上升趋势;术后4、68、、12周,缩窄组小鼠动脉收缩压(SBP)、动脉舒张压(DBP)、左心室收缩压(LVSP)、左心室舒张末压(LVEDP)显著增加(P<0.05);术后8周,缩窄组小鼠表现为离心性肥厚,左心室收缩末期、舒张末期内径(LVESd;LVEDd)显著增加(P<0.05);术后12周,缩窄组小鼠出现失代偿性心力衰竭,左心室射血分数(EF%)、左心室压力上升和下降最大速率(dp/dtmax;dp/dtmin)显著降低(P<0.05),与8周缩窄组比较,12周缩窄组SBP、DBP、LVSP、LVEDP显著降低(P<0.05)。结论通过主动脉弓缩窄,可以建立稳定的小鼠压力超负荷诱导左室向心性肥厚致心衰的动物模型,类似人类心肌肥厚向心衰发展的病理过程,是用于临床研究的一种较理想动物模型。Objective To establish the transverse aortic constriction （TAC） mouse model through microsurgery and to explore the changed tendency of heart structure and function. Methods 135 KM mice randomly were divided into two groups： transverse aortic constriction （TAC） group （ n = 75 ） and sham-operation （SH） group （ n = 60）. Echocardiographic assessments with a 15 MHz HF linear array transducer, hemodynamic determination, heart weight and histological examination were performed before and at 1, 4 , 6, 8, 10 and 12 weeks after surgery. The cause of death was analyzed. Results （ 1 ） The success rate of TAC was 88% . （2）Compared with SH, Pwsth, Pwdth, LVMI of TAC group at 4 week increased significantly（ P 〈 0.05）and above index showed a lightly progressive increase at 6,8,12 week. SBP,DBP,LVSP,LVEDP of TAC group at 4,6,8,12 week were increased significantly （ P 〈 0.05 ） and appeared concentric hypertrophy. At 8 week, LVESd, LVEDd of TAC group were significantly increased （P 〈 0.05） and appeared eccentric hypertrophy. At 12 week, EF% ,dp/dtmax; dp/dtmin were decreased （ P 〈 0.05）. Compared with 8 week TAC group, SBP,DBP,LVSP,LVEDP of TAC group at 12 week werer significantly decreased （ P 〈 0.05）. It showed the heart failure. Conclusion A TAC model could be established in KM mice. LV from hypertrophy to heart failure by pressure overload have developed. This model is similar to pathogenetic process of human heart disease.

关 键 词：主动脉弓缩窄 压力负荷 左室肥厚 心力衰竭 

分 类 号：Q463[生物学—生理学]