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|本期目录/Table of Contents|

环孢菌素A拮抗心肌缺血/再灌注损伤的作用

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2014年第1期
页码:
15-20
栏目:
基础研究
出版日期:
2013-12-02

文章信息/Info

Title:
Cyclosporine protects against myocardial ischemia/reperfusion injury
作者:
尹巧香1王 恒2裴志勇3赵玉生4
(空军总医院:1.干部病房心内科,2.神经内科,北京 100142;3.北京军区总医院干部病房一科,北京100700;4.解放军总医院老年心血管病研究所,北京 100853)
Author(s):
YIN Qiao-xiang1 WANG Heng2 PEI Zhi-yong3 ZHAO Yu-sheng4
(1.Department of Geriatric Cardiology, 2.Department of Neurology, General Hospital of Air Force, Beijing 100142, China; 3.Department of Geriatric Cardiology, General Hospital, Beijing Military Area Command, Beijing 100700, China; 4.Institute of Geriatric Cardiology, PLA General Hospital, Beijing 100853, China)
关键词:
环孢菌素A心肌缺血/再灌注损伤他可英司线粒体小型猪
Keywords:
cyclosporin A myocardial ischemia/reperfusion injury FK-506 mitochondria swine
分类号:
R979.5
DOI:
-
文献标识码:
A
摘要:
目的:研究环孢菌素A(CsA)拮抗小型猪心肌缺血/再灌注损伤(MI/RI)的作用及可能的机制。方法:经皮球囊封堵冠状动脉左前降支制备小型猪MI/RI模型。将存活的动物随机分为3组:即对照组(n=4)、CsA组(n=6)及他可英司(FK-506)组(n=6),分别静滴生理盐水100 ml、25 mg/kg CsA及1 mg/kg FK-506。所有动物均经90 min缺血和3 h再灌注。通过病理检查评估心肌梗死(MI)面积。用免疫组化染色法检测心肌细胞凋亡。用透射电子显微镜观察各组心肌细胞线粒体的形态。结果:CsA组MI的面积比对照组[(7.5±0.6) cm2 vs. (10.5±2.6) cm2]和FK-506组[(7.5±0.6) cm2 vs. (9.6±2.7) cm2]明显减少(P<0.01);CsA组心肌细胞的凋亡率(%)比对照组[(11.9±1.88)% vs. (22.3±1.66)%]和FK-506组[(11.9±1.88)% vs. (19.2±1.82)%]明显下降(P<0.01)。透射电子显微镜检查显示,CsA组能维持线粒体的形态,线粒体坍塌的百分率为(20%±7%),比对照组(53%±12%)和FK-506组(47%±9%)明显减少(P<0.01)。结论:CsA可能对MI/RI具有拮抗作用,其机制可能是通过抑制线粒体膜通透性转换孔(mPTP),保持线粒体形态完整而实现,此种效应不依赖于钙调磷酸酶抑制途径。
Abstract:
AIM:To evaluate the effects and mechanisms of cyclosporin A (CsA) in protecting against myocardial ischemia/reperfusion injury in a swine model. METHODS: Models were established by coronary angioplasty percutaneous balloon occlusion of the left anterior descending artery (LAD). Swine that survived after myocardial ischemia/reperfusion were divided into three groups: control (n=4), CsA (n=6) and FK-506 (n=6). The three groups received, respectively, saline vehicle 100 ml, 25 mg/kg CsA and 1 mg/kg FK-506. All animals underwent 90 min of regional ischemia and 3 h of reperfusion. Myocardial infarct size and apoptotic cell death were determined by pathological assessment and immunohistopathology. Transmission electron microscopy was used to evaluate morphologic differences in the mitochondria between the groups. RESULTS: Infarct size in CsA group was significantly reduced compared with that in control group [(7.5±0.6) cm2 vs.(10.5±2.6) cm2, P<0.01] and FK-506 group [(7.5±0.6) cm2 vs.(9.6±2.7) cm2, P<0.019]. Apoptotic index in CsA group was also attenuated compared with that in control group [(11.9±1.88)% vs.(22.3±1.66)%, P<0.01] and FK-506 group [(11.9±1.88)% vs.(19.2±1.82)%, P<0.01]. Transmission electron microscopy revealed a preservation of normal mitochondrial morphology and a reduction in the percentage of disrupted mitochondria in CsA group (20%±7%) compared with those in control group (53%±12%) and FK-506 group (47%±9%). CONCLUSION: Cyclosporine A-induced mPTP inhibition preserves mitochondrial morphology after myocardial ischemia/reperfusion and limits myocyte necrosis and apoptosis. These effects are independent of calcineurin inhibition.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期:2013-07-04.基金项目:国家高技术研究发展(863)计划项目资助(2006AA02A105) 作者简介:尹巧香,副主任医师,博士 Email:zmyyqx-20041129@163.com
更新日期/Last Update: 2014-01-20