环孢菌素A拮抗心肌缺血/再灌注损伤的作用  

Cyclosporine protects against myocardial ischemia /reperfusion injury

作　　者：尹巧香[1] 王恒[2] 裴志勇[3] 赵玉生[4] 

机构地区：[1]空军总医院干部病房心内科,100142 [2]空军总医院神经内科北京,100142 [3]空军总医院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

出　　处：《心脏杂志》2014年第1期15-20,共6页Chinese Heart Journal

基　　金：国家高技术研究发展(863)计划项目资助(2006AA02A105)

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)cm2vs.(10.5±2.6)cm2]和FK-506组[(7.5±0.6)cm2vs.(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 coro- nary 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 rain of regional ischemia and 3 h of reperfusion. Myocardial infarct size and apoptotic cell death were determined by pathological assessment and immuno- histopathology. Transmission electron microscopy was used to evaluate morphologie differences in the mi- tochondria between the groups. RESULTS： Infarct size in CsA group was significantly reduced compared with that in control group [（7.5 ±0.6） em2 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 mitochon- dria 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 mor- phology after myocardial ischemia/reperfusion and limits myocyte necrosis and apoptosis. These effects are independent of calcineurin inhibition.

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 

分 类 号：R979.5[医药卫生—药品]