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兔甲亢性心肌病不同左室构型心肌细胞的凋亡

Cardiomyocyte apoptosis of different left ventricular geometric patterns in rabbits with hyperthyroid cardiomyopathy
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摘要 目的:观察兔甲亢性心肌病不同左室构型心肌细胞的凋亡情况及相关bcl-2、bax蛋白表达的变化。方法:将30只新西兰纯种白兔分为实验组(n=20)和对照组(n=10),实验组兔每日腹腔注射左旋甲状腺素(45μg/kg体质量)共4周建立甲亢动物模型,对照组兔每日腹腔注射同等剂量的生理盐水共4周。4周后,对两组兔行常规超声心动图参数测定。实验组依据超声参数又分为向心性肥厚亚组(CH亚组)和离心性肥厚亚组(EH亚组)。第4周末处死所有兔,取心肌组织,在透射电镜下观察心肌细胞,应用原位末端标记法标记凋亡的心肌细胞,应用免疫组织化学染色法检测bcl-2、bax蛋白的表达。结果:①透射电镜观察CH亚组和EH亚组均有大量的凋亡细胞,且凋亡指数(AI)显著高于对照组(均P<0.01),EH亚组的AI又显著高于CH亚组(P<0.01)。②CH亚组和EH亚组bcl-2蛋白的表达显著低于对照组(均P<0.01),EH亚组又显著低于CH亚组(P<0.01);CH亚组和EH亚组bax蛋白的表达显著高于对照组(均P<0.01),EH亚组又显著高于CH亚组(P<0.01)。CH亚组和EH亚组bcl-2/bax的比值显著低于对照组(均P<0.01)。结论:兔甲亢性心肌病不同左室构型具有不同程度的心肌细胞凋亡,说明细胞凋亡机制参与了该病的病理过程,其作用与下调bcl-2蛋白的表达、上调bax蛋白的表达有关。 AIM: To study cardiomyocyte apoptosis and the expressions of bcl2 and bax protein in levo thyroxineinduced cardiomyopathy in rabbits with different patterns of left ventricular geometric models. METHODS: Thirty New Zealand purebred rabbits were stochastically divided into experimental group (n = 20) and control group (n = 10). Hyperthyroidism models were established by peritoneal injection of levothyroxine (LThy) in experimental group [45μg/(kg .day)] for 4 weeks. The same dose of saline was given to rabbits in the control group for 4 weeks. Conventional eehocardiographie parameters were ob tained at the end of the fourth week in both groups and according to the changes of ultrasound parame ters, the rabbits of experimental group were divided into two subgroups : concentric hypertrophy ( CH ) and eccentric hypertrophy (EH). All rabbits were executed 4 weeks later, myocardial tissue was ob tained and eardiomyocytes were observed by transmission electron microscope. Apoptotic cardiomyocytes were detected using terminal deoxynucleotidyl transferasemediated dUTP nick end labeling (TUNEL) method and the expressions of bcl2 and bax protein were determined by immunohistochemical method using mean absorbanee. RESULTS: Many apoptotic cardiomyocytes were found in CH subgroup and EH subgroup by electron microscope, whereas no apoptotic cardiomyocytes were seen in the control group.Compared with that in the control group, the index of apoptotic cardiomyocytes increased significantly in both subgroups (P 〈0. 01 ). The index in apoptotic cardiomyocytes of the EH subgroup was higher than in the CH subgroup (P 〈0. 01 ). Compared with the control group, bcl-2 protein expression was signifi- cantly lower in the CH subgroup and EH subgroup (P 〈 0. 01 ) and bcl-2 protein expression in the EH subgroup was lower than in the CH subgroup (P 〈 0. 01 ). The expression of bax protein was significantly higher in the CH subgroup and EH subgroup (P 〈 0. 01 ) and bax protein expression in the EH subgroup was higher than in the CH subgroup (P 〈 0.01 ) ; bcl-2/bax was significantly lower in CH subgroup and EH subgroup ( P 〈 0. 01 ). CONCLUSION : The degree of cardiomyocyte apoptosis is different in differ- ent patterns of left ventricular geometric models of levothyroxine-induced cardiomyopathy, indicating that cardiomyocyte apoptosis is an important pathological mechanism of levothyroxine-induced cardiomyopa- thy. The effect may be related to the downregulation of bcl-2 protein expression and upregulation of bax protein expression.
出处 《心脏杂志》 CAS 2013年第1期38-42,共5页 Chinese Heart Journal
基金 辽宁省科技厅科技计划项目资助(2009225009-7)
关键词 细胞凋亡 甲状腺功能亢进 心肌疾病 apoptosls hyperthyroldmm cardiomyopathies rabbit
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参考文献11

  • 1Ganau A, Devereux RB, Roman M J, et al. Patterns of left ventricu- lar hypertrophy and geometric remodeling in essential hypertension[J].Am Coll Cardiol, 1992, 19(7) :1550-1558.
  • 2Litwin SE, Katz SE, Morgan JP, et al. Serial echocardiographic as- sessment of left ventricular geometry and function after large myocar- dial infarction in the rat[ J]. Circulation, 1994, 89( 1 ) :345 -354.
  • 3Sabbah HN. Apoptotic cell death in heart failure [ J ]. Cardiovasc Res, 2000, 45(3) :704 -712.
  • 4Dfez J, GonzOlez A, L6pez B, et al. Mechanisms of disease:patho- logic structural remodeling is more than adaptive hypertrophy in hy- pertensive heart disease [ J ]. Nat Clin Pract Cardiovasc Med, 2005, 2(4) :209 -216.
  • 5蔡辉,修春英,郭郡浩,沈思钰,赵智明.川芎嗪对溶血磷脂酸诱导的心脏成纤维细胞增殖及胶原合成的影响[J].医学研究生学报,2008,21(1):31-33. 被引量:18
  • 6GonzOlez A, L6pez B, D[ez J, et al. Fibrosis in hypertensive heart disease : role of the renin-angiotensin-aldosterone system [ J ]. Med Clin North Am, 2004, 88( 1 ) :83 -97.
  • 7Klein I, Ojamaa K. Thyrotoxic cardiac disease [ J ]. Curr Heart Fail Rep, 2008, 5(3) :170 - 176.
  • 8陈玲,樊继援.甲亢性心脏病形成机制的研究进展[J].临床荟萃,2008,23(2):151-152. 被引量:12
  • 9礼广森,任卫东,张卓,崔洪岩,夏稻子,马春燕.定量组织速度成像评价阿霉素心脏毒性左心室功能的变化与心肌细胞凋亡相关性的研究[J].中国超声医学杂志,2007,23(4):244-246. 被引量:2
  • 10Brooks C, Dong Z. Regulation of nfitochondrial morphological dy- namics during apoptosis hy Bcl-2 family proteins: a key in Bak[J]. Cell Cycle, 2007, 6(24) :3043 -3047.

二级参考文献31

  • 1修春英,蔡辉.溶血磷脂酸与缺血性心脏病[J].医学研究生学报,2006,19(2):172-174. 被引量:3
  • 2修春英,蔡辉,赵智明,郭郡浩,金洁.溶血磷脂酸对心脏成纤维细胞增殖和胶原合成的影响[J].医学研究生学报,2006,19(7):589-591. 被引量:4
  • 3Kremer LC,Vam-Dalen EC.Offringa M.et al. Anthracycaline-induced clinical heart failure-up study. J Clin Oncol, 2001,19(1): 191-196.
  • 4Andersson B, Wagstein F, Caidahl K. et al. Early changes in longitudinal performance predicl future improvement in global left ventricular function during long term β-adrenergic blockade. Heart. 2000.84 (6) : 599-605.
  • 5Maeda A,HondaM,Kura Mochi T,et al. Doxorubicin cardiotoxicity:diastolic cardiac myocyle dysfunction as a result of impaired calcium handling in isolated cardiac myocytes. Jpn Cite J,1998.62(7):505-512.
  • 6Singnal PK, Iliskovic N. Doxorubicin induced cardiomyopathy. N Engl J Med.1998,339(13):900-905.
  • 7Nakamura T,Ueda Y,Juan Y,et al. Fas-mediated apoptosis in adriamycin induced cardiomyopathy in rats: in vivo study. Circulation.2000. 102(5) :572-578.
  • 8Ray R,Chen G, Velde CV,et al. Bnlp3 heterodimerizes with bcl-2/bcl-1 X1 and induces cell death independent of a bcl-2 homology 3(BH3)domain at both mitoehondrial and nonmitochondrial sites. J Biol Chem. 2000, 14,275 (2): 1439-1448.
  • 9Cappola AR, Fried LP, Arnold AM. Thyroid status, cardiovascular risk, and mortality in older adults[J]. JAMA, 2006,295(9) :1033-1041.
  • 10Fazio S, Palmieri EA, Lombardi G, et al. Effects of thyroid hormone on the cardiovascular system[J]. Recent Prog Horm Res,2004,59:31-50.

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