^(99m)Tc-MIBI评价心肌缺血/再灌注线粒体膜功能损伤的实验研究  

Assessment of mitochondrial dysfunctions in myocardial ischemia/reperfusion injury with 99m Tc MIBI

作　　者：曾骏[1,2,3] 赵惠扬[1,2,3] 林祥通[1,2,3] 谢文晖 张莉华 俞志昌[1,2,3] 刘平安 姚瑞明[1,2,3] 

机构地区：[1]上海医科大学核医学研究所 [2]上海市胸科医院核医学科 [3]上海市心血管病研究所

出　　处：《中华核医学杂志》1998年第1期17-21,共5页Chinese Journal of Nuclear Medicine

摘　　要：目的分析９９ｍＴｃ甲氧基异丁基异腈（ＭＩＢＩ）评价心肌缺血再灌注线粒体膜功能损伤的可能性。方法经分离鼠心肌线粒体，用氯化钙和（或）氯化钠模拟线粒体再灌注损伤，冠状动脉结扎制作犬急性和慢性心肌缺血模型。用线粒体内膜孔阻滞剂环孢素Ａ和钙钠交换拮抗剂地尔硫或硫酸镁，以及钙拮抗剂硝苯地平介入进行体外９９ｍＴｃＭＩＢＩ线粒体结合分析和体内显像研究。结果体外可逆性再灌注损伤能抑制线粒体摄取９９ｍＴｃＭＩＢＩ，并延长结合反应时间。体内再灌注损伤心肌能加速清除９９ｍＴｃＭＩＢＩ。体外和体内环孢素Ａ加地尔硫能改善可逆性功能损伤心肌线粒体摄取９９ｍＴｃＭＩＢＩ，体内用硝苯地平可防止再灌注损伤，能延迟缺血心肌清除９９ｍＴｃＭＩＢＩ。药物介入后，局部心肌摄取９９ｍＴｃＭＩＢＩ明显高于１２５Ｉ微球灌注，并且９９ｍＴｃＭＩＢＩ清除过程与Ｐ糖蛋白高表达的肝脏完全不同。Purpose To evaluate the possibility of using 99m Tc MIBI as the tracer of mitochondrial functions Methods Intact mitochondria were prepared from SD rat hearts by differential centrifugation The acute and chronic myocardial ischemia of dogs were made by surgery The 99m Tc MIBI mitochondria binding studies in vitro in the presence of CaCl 2 or (and) NaCl to mimic reperfusion injury and 99m Tc MIBI myocardial imaging studies in vivo were undertaken with or without intervenient drugs, including cyclosporin A (a inhibitor of mitochondrial inner membrane's pore), diltiazem or magnesium sulfate (the Ca 2+ /2Na + exchanger inhibitors) and nifedipine (the calcium channel antagonist) Results Though % 99m Tc MIBI binding in vitro was blocked in the present of CaCl 2 on (and) NaCl, the full or partial recovery of % 99m Tc MIBI achieved by adding cyclosporin A plus diltiazem or by prolonging the duration of binding depending on CaCl 2 concentration Also, cyclosporin A plus diltiazem could enhance the uptake of 99m Tc MIBI but not that of 125 I microsphere perfusion in ischemic myocardium The clearance of 99m Tc MIBI from ischemic regions was retarded if the reperfusion injury was prevented by administration of nifedipine before dobutamine stress The clearance of 99m Tc MIBI in ischemic myocardium was different from that of livers where the P glycoprotein gene is highly expressed Conclusions The uptake and clearance of 99m Tc MIBI could be affected by myocardial mitochondrial functions

关 键 词：心肌缺血 再灌注损伤 线粒体膜功能 ^99MTC-MIBI 

分 类 号：R542.204[医药卫生—心血管疾病] R817.42[医药卫生—内科学]