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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(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2012年第2期
页码:
168-172
栏目:
基础研究
出版日期:
2012-04-25

文章信息/Info

Title:
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
(第四军医大学:1.西京医院心血管外科,2.药学院药理学教研室,3.基础医学院生理学教研室,陕西 西安 710032)
Author(s):
DANG Hai-zhou1 LI Ming-kai2 Xu Ming3 YU Shi-qiang1 LUO Xiao-xing2
(1.Department of Cardiovascular Surgery, Xijing Hospital, 2.Department of Pharmacology, School of Pharmacy, 3.Department of Physiology, School of Basic Medical Sciences, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
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
Keywords:
animal model aortic arch constriction isoprenaline hydrochloride heart failure mouse
分类号:
R541.61
DOI:
-
文献标识码:
A
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。
Abstract:
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), sham-operation group (A), IPH injection-induced model group [15 mg/(kg·day), 11 days (B)] and aortic arch constriction-induced model group (C). Heart weight to body weight ratio (HW/BW), left ventricular internal diameter at end-diastole (LVEDD), left ventricular internal diameter at end-systole (LVEDS), left ventricular ejection fraction (EF) and LV fractional shortening (FS) were measured after 8 weeks. The expression levels of ANP, BNP, and α-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.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期:2011-11-14.基金项目:国家自然科学基金课题资助(81070198,30800310) 通讯作者:俞世强,主任医师,主要研究方向为微创心脏外科Emai:yushiq@fmmu.edu.cn 共同通讯作者:罗晓星,教授,主要研究方向为心脏交感神经组胺和耐药细菌反义药物研究Email:xxluo3@fmmu.edu.cn 作者简介:党海舟,硕士生 Email:chyne219@163.com 共同第一作者:李明凯,讲师,博士 Email:mingkai@fmmu.edu.cn
更新日期/Last Update: 2012-04-01