中文摘要：

目的探讨外周苯二氮革受体（peripheral benzodiazepine receptor，PBR）在调控心肌线粒体通透性转换（mitochondrial permeability transition，MPT）中的作用。方法分离SD大鼠心肌线粒体，电镜观察其形态证实线粒体结构完整性。将线粒体分别和不同浓度（50，100，200μmol·L^-1）的PBR拮抗剂PK11195孵育，部分线粒体和100mmol·L^-1 PK11195孵育之前5min加入5μmol·L^-1MPT抑制剂环孢菌素A（CsA组）。不给任何处理的线粒体为阴性对照（Con组），单纯给150μmol·L^-1Ca^2＋作阳性对照（Ca^2＋组）。分光光度法测520nm处吸光度的改变反映MPT变化，电镜观察线粒体超微结构改变，Western blot检测线粒体细胞色素C（Cyto C）释放。结果PK11195剂量依赖性诱发MPT，不同浓度组间比较差异有显著性（P＜0．05，P＜0．01）；PK11195导致线粒体出现空泡变性、线粒体肿胀、线粒体脊膜破裂，Cyto C释放明显增多（vs Con组，P＜0．01）；CsA能阻断PK11195的上述作用，CsA组线粒体超微结构基本完好。线粒体Cyto C释放较少（vs 100μmol·L^-1组，P＜0．05）。结论PBR参与调控大鼠心肌MPT，其拮抗剂PK11195可剂量依赖性诱导心肌MPT，导致线粒体超微结构损伤和线粒体Cyto C释放。

英文摘要：

Aim To investigate the role of peripheral benzodiazepine receptor in rat cardiac mitochondrial permeability transition. Methods The isolated rat cardiac mitochondria were incubated with different doses （50,100,200 μmol · L^-1 ） of PBR antagonist [ 1-（2- chlorophenyl-N-methyl-l-methylpropyl ） -3-isoquinolinecarboxamide （ PK 11195 ）. In additional group （ CsA group）, 5μmol · L^-1 cyclosporine A （CsA）, an inhibitor of MPT was added 5 minutes before the addition of 100 μmol · L^-1 PK 11195. Negative control group （Con group） was given none treatment. Positive control group（Ca^2＋ group） was given 150 μmol · L^-1 CaC12. The absorbanceat 520 nm （ Abs 520 nm ） was monitored with a split-beam spectrophotometer at 30℃ for 10 min. The mitoehondrial ultrastructure was assessed by transmission electron microscopy. Mitoehondrial cytochrome C release was demonstrated by Western Blotting. Results PKI 1195 triggered large-amplitude mitochondrial swelling in a dose dependent manner（vs Con group,P 〈0. 05, P 〈0. 01 ）, There were significant differences among different dose of PK 11195 （ P 〈 0. 05 ） ; PK11195 caused mitochondria ultrastructural abnormalities, the release of CytoC from mitochondria into the cytosol （vs Con group, P 〈 0. 01 ） ; In CsA group, most of mitochondria displayed the characteristic ultrastructure of the intact organelle, there was less release of mitochondria cytochrome C from mitochondria （vs 100 μmol · L^-1 group, P 〈 0. 05）. Conclusion PBR is involved in the regulation of MPT, which can regulate cardiac mitochondria injury, appears of a novel target for cardioprotection.