内皮素受体拮抗剂BMS-182874对大鼠心肌缺血再灌注损伤的保护作用  

Effects of Endothelin A Receptor Antagonist BMS-182874 on Ischemia-Reperfusion Injury in Isolated Rat Hearts

作　　者：陈美芳[1] 江俊麟[2] 李元建[2] 杨天伦[1] 

机构地区：[1]中南大学湘雅医院心内科 [2]中南大学药学院药理学系,湖南省长沙市410008

出　　处：《中国动脉硬化杂志》2004年第1期31-34,共4页Chinese Journal of Arteriosclerosis

摘　　要：为观察选择性内皮素A受体拮抗剂BMS 182 874对离体灌注心脏缺血再灌损伤的影响 ,并进一步探讨其可能的作用机制。按照Langendorff方式灌注离体大鼠心脏 ,全心缺血 30min后再灌注 30min诱导急性心肌缺血模型。给予BMS 182 874 (10 μmol/L或 5 0 μmol/L)持续灌注离体心脏 ,连续记录心功能 ,检测冠状动脉流出液中的肌酸激酶和心肌组织中的肿瘤坏死因子α含量。结果发现 ,与对照组相比 ,缺血再灌注组心功能显著下降 ,左心室内压和左心室内压最大变化率 (±dp/dtmax)、冠状动脉流量明显降低 (P <0 .0 1) ,肌酸激酶 (2 3.9± 2 .2比 2 17.5± 14 .1,P<0 .0 1)以及心肌组织中肿瘤坏死因子α含量明显增加 (6 4 5± 4 5比 192 6± 14 1,P <0 .0 1) ,而 10 μmol/L和 5 0 μmol/L的BMS 182 874显著减轻缺血后心功能的损害 ,升高左心室内压和左心室内压最大变化率 (±dp/dtmax) (P <0 .0 1) ,同时降低肌酸激酶 (185± 14和 14 3± 11,与缺血再灌注组相比P <0 .0 5和P <0 .0 1)和心肌组织中的肿瘤坏死因子α含量 (12 2 2± 6 7和 110 8± 5 7,与缺血再灌注组相比P <0 .0 1)。结果提示 ,内皮素A受体拮抗剂能显著减轻心肌缺血再灌注损伤 ,其保护作用可能与抑制心肌组织中肿瘤坏死因子α生成有关。Aim To investigate the effect of selective endothelin A receptor (ETA)antagonist BMS-182874 on myocardial ischemia-reperfusion (I-R) injury in isolated rat hearts. Methods The isolated hearts were perfused in a Langendorff mode and acute myocardial ischemic model was induced by 30 min of global ischemia and 30 min of reperfusion. The effects of ETA receptor antagonist BMS-182874 (10 μmol/L, 50 μmol/L) on heart function during reperfusion, the release of cardiac creatine kinase (CK) in the coronary effluent and the content of myocardial tumor necrosis factorα (TNF-α) were analyzed. Results 30-minute global ischemia caused a dramatic decrease in myocardial function, as shown by decreasing LVP, ±dp/dt max ,, CF (P<0.01) and increasing CK release (23.9±2.2 vs 217.5±14.1, P<0.01) and myocardial TNF-α content (645±45 vs 1 926±141, P<0.01). However, treatment with 10 μmol/L and 50 μmol/L BMS-182874 significantly attenuated the ischemia-induced myocardial injury, increased LVP, ±dp/dt max , and reduced the release of CK (185±14, 143±11, compared with ischemia/reperfusion group, P<0.05, P<0.01 respectively) and the TNF-αcontent in myocardial tissues (P<0.01), but had no effect on HR and CF (1222±67, 1108±57, compared with ischemia/reperfusion group, P<0.01). Conclusions These findings suggest the cardioprotective effects afforded by ETA receptor antagonist BMS-182874 may be related to inhibition of myocardial TNF-αproduction.

关 键 词：药理学 内皮素受体拮抗剂的药理作用 大鼠离体心脏灌注法 肿瘤坏死因子A 肌酸激酶 缺血再灌注 心肌损伤 

分 类 号：R962[医药卫生—药理学]