环孢菌素A拮抗心肌缺血／再灌注损伤的作用

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100ml、25mg／kgCsA及1mg／kgFK-506。所有动物均经90rain缺血和3h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）cm。粥．（10．5±2．6）cm。]和FK-506组[（7．5±0．6）cm。掷．（9．6±2．7）cm。]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）％郴．（22．3±1．66）％]和FK-506组[（11．9±1．88）％郴．（19．2±1．82）％]明显下降（JP〈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。

Cyciosporine protects against myocardial ischemia/reperfusion injury

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.