主动脉弓缩窄术和腹腔注射IPH致小鼠慢性心衰两种模型的比较和评价  

Evaluation of congestive heart failure mouse models induced by surgery or drugs

作　　者：党海舟[1] 李明凯[2] 徐明[3] 俞世强[1] 罗晓星[2] 

机构地区：[1]第四军医大学西京医院心血管外科,陕西西安710032 [2]第四军医大学药学院药理学教研室,陕西西安710032 [3]第四军医大学基础医学院生理学教研室,陕西西安710032

出　　处：《心脏杂志》2012年第2期168-172,共5页Chinese Heart Journal

基　　金：国家自然科学基金课题资助(81070198;30800310)

摘　　要：目的:比较和评价主动脉弓缩窄术与腹腔注射盐酸异丙肾上腺素(isoprenaline hydrochloride,IPH)两种方法所建立的小鼠慢性心力衰竭(chronic heart failure,CHF)模型的差异及优缺点。方法:将24只6～8周雄性C57BL小鼠随机分为4组,即正常对照组(N组)、假手术组(A组)、药物模型组[腹腔注射15 mg/(kg.d)的IPH,B组]和手术模型组(主动脉弓缩窄术,C组),每组6只小鼠(n=6)。采用主动脉弓缩窄术和腹腔注射IPH建立小鼠CHF模型。分别于术后8周及连续腹腔注射IPH 11 d后8周,测量心脏质量/体质量比(HW/BW)、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVEDS)、左室射血分数(LVEF)和短轴缩短率(FS)。使用PCR及琼脂糖凝胶电泳分析的方法检测心肌组织中心房钠尿肽(atrial natriuretic peptide,ANP)、脑尿钠肽(brain natriuretic peptide,BNP)、肌球蛋白重链(α-MHC)表达的水平,并行病理学检查。结果:主动脉弓缩窄术与腹腔注射IPH均成功地建立小鼠CHF模型。与N组比较,B组LVEDS增高36.06%,LVEF和FS分别降低24.88%和29.22%(P<0.01),单位面积下心肌细胞的数目减少24.80%(P<0.01)。与N组比较,C组的HW/BW明显升高(P<0.01),LVEDD和LVEDS分别增高27.42%和54.81%,LVEF、FS分别降低37.40%和42.17%(P<0.01),单位面积下心肌细胞的数目减少48.39%(P<0.01)。C组较B组HW/BW明显升高(P<0.01),单位面积下心肌细胞的数目减少更为显著(P<0.01)。结论:C组与B组相比,可以更良好地模拟后负荷增高导致的心力衰竭(HF),其病理生理过程与高血压导致的HF更接近,且与N组相比显著性较好,是理想的HF模型。AIM： To compare two chronic heart failure （CHF） mouse models established, respectively, by aortic arch constriction or by isoprenaline hydrochloride （IPH）. METHODS： Adult C57BL mice were randomly divided into four groups： natural control group （N） injection-induced model group [ 15 mg/（kg·day）, 11 days （B） ] model group （C）. Heart weight to body weight ratio （HW/BW）,, sham-operation group （A）, IPH and aortic arch constriction-induced left ventricular internal diameter at end-diastole （LVEDD）, left ventricular internal diameter at end-systole （LVEDS）, left ventricular ejec-tion fraction （EF） and LV fractional shortening （FS） were measured after 8 weeks. The expression levels of ANP, BNP, and ct-MHC in heart tissues and the size of cardiomyocytes were also observed. RESULTS： Both IPH injection and aortic arch constriction successfully established experimental models of CHF. Compared with those in the N group, LVEDS increased by 36.06%, EF and FS decreased by 24. 88% and 29.22%, respectively （ P 〈 0. 05 ）, and cell numbers/1 mm2 increased by 24. 80% （P 〈 0. 01 ） in group B. HW/BW significantly increased （ P 〈 0. 01 ）, LVEDD and LVEDS increased, respectively, by 27.42% and 54. 81%, LVEF and FS decreased by 37.40% and 42. 17%, respectively （P 〈0. 01 ）, and cell numbers/1 mm2 increased by 48.39% （P 〈0. 01 ） in group C. HW/BW and cell numbers/1 mm2 in group C significantly increased compared with those in group B （ all P 〈 0. 01 ）. CONCLUSION： CHF mouse model induced by aortic arch constriction may well mimic the pressure overload-induced heart failure, and its pathophysiological development is similar to the pressure overload-induced heart failure. CHF mouse model induced by aortic arch constriction is an ideal model of CHF over IPH injection method.

关 键 词：动物模型 主动脉弓缩窄术 盐酸异丙肾上腺素 心力衰竭 小鼠 

分 类 号：R541.61[医药卫生—心血管疾病]