摘要
目的探讨环孢素A(cyclosporine A,CsA)是否逆转野百合碱(monocrotaline,MCT)诱导的右心室重构及其作用机制的初步探讨。方法雄性SD大鼠随机分正常对照组,MCT模型组,CsA低、高剂量组(0.33和1mg·kg-1)。MCT造模后14～21d给CsA(ig,bid)。造模22d右心导管术检测右室收缩压(RVSP);称右室自由壁(RV)及左心室加室间隔(LV+SEP)重,计算右心肥大指数(RVHI=RV/LV+SEP);光镜及电镜观察右室结构变化;免疫组化检查右室心肌细胞PCNA的表达。结果CsA逆转MCT所引起RVSP、RVHI的升高(P<0.05或P<0.01)、右室心肌细胞肥大、线粒体肿胀变性及PCNA抗原的过表达。高剂量CsA作用更明显。结论CsA(1mg·kg-1 ig,bid)能明显逆转MCT诱导的右室重构,其机制可能与降低右室后负荷及抑制右室心肌细胞肥大有关。
Abstract
OBJECTIVE To explore the effect and the preliminary mechanism of cyclosporine A (CsA) on the right ventricle remodeling caused by monocrotaline (MCT). METHODS Thirty-six Sprague-Dawley male rats were randomly divided into normal control group,MCT group,low and high dose of CsA treatment group. Rats were given a single dose of MCT (50 mg·kg-1, sc) for inducing the right ventricle remodeling. CsA (0.33 and 1 mg·kg-1,bid,ig) was administered from day 14 to day 21 respectively. The right ventricle (RV) and the left ventricle with septum (LV+SEP) were weighed separately. RVHI was measured as RV/(LV+SEP). The histological examination of RV were executed by light microscope. The ultramicrostructure of the RV tissues was observed under the transmission electron microscope. Immunohistochemical analysis was performed on paraffin-embedded RV tissue using the anti-proliferating cell nuclear antigen (PCNA) primary antibodies. RESULTS CsA significantly inhibited the increase of RV systolic pressure and RVHI, compared with MCT group (P<0.05 or P<0.01). Histological examination revealed that CsA effectively prevented RV cardiomyocytes hypertrophy. The transmission electron microscope examination demonstrated that the swollen and misshapen mitochondria in RV cardiomyocytes induced by MCT was improved by CsA. CsA effectively reduced the PCNA expression in RV cardiomyocytes. The effect of high dose CsA was more significant (P<0.01). CONCLUSION CsA (1 mg·kg-1,ig,bid) can improve the RV remodeling effectively in MCTtreated rats. The mechanism may be related to the reduction of RV systolic pressure and the inhibition of the cardiac hypertrophy.
关键词
环孢素A /
心肌重构 /
心肌肥大 /
野百合碱
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Key words
cyclosporine A /
ventricular remodeling /
cardiac hypertrophy /
monocrotaline
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杨丹莉;李晓辉;张海港;杨晓娇;郝雪琴;苏敏.
环孢素A逆转野百合碱所诱导的右心室重构[J]. 中国药学杂志, 2009, 44(14): 1070-1073
YNG Dn-li;LI Xio-hui;ZHNG Hi-gng;YNG Xio-jio;HO Xue-qin;SU Min.
Effect of Cyclosporine A on the Right Ventricle Remodeling in Monocrotaline-Treated Rats [J]. Chinese Pharmaceutical Journal, 2009, 44(14): 1070-1073
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参考文献
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脚注
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基金
国家自然科学基金资助项目(30371768,30672641);重庆市自然科学基金资助项目(20048256)
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