乳化异氟醚后处理对兔在体心脏缺血/再灌注损伤的保护作用

Protective effects of emulsified isoflurane postconditioning on myocardium against ischemia reperfusion injury in rabbits

目的观察乳化异氟醚后处理对兔在体心肌缺血/再灌注损伤的影响并探讨线粒体ATP敏感性钾通道(KATP)在其中的作用。方法76只♂新西兰白兔,建立心脏30min缺血/180min再灌注损伤模型,随机分为10组:缺血对照组(CON,n=8)、缺血后处理组(IPO,n=8)、1.0MAC吸入异氟醚后处理组(ISO,n=8)、1.0MAC乳化异氟醚后处理组(EPO,n=8)、脂肪乳组(INT,n=7)、Glibenclamide组(GLI,非选择性KATP通道阻滞剂,0.3mg.kg-1,n=7)、5-hydroxy-decanoate组(5-HD,线粒体KATP通道阻滞剂,5mg.kg-1,n=8)、0.3mg.kg-1GLI+1.0MAC EPO组(GLI+EPO,n=8)、5mg.kg-15-HD+1.0MAC EPO组(5-HD+EPO,n=7)、Dimethylsulfoxide组(DMSO,GLI的溶剂,n=7)。观察血流动力学指标,缺血区(AAR)重、梗死区(IS)重,心肌梗死面积(以IS/AAR表示),再灌注180min测定血清肌酸激酶(CK)、乳酸脱氢酶(LDH)活性。结果与CON组比较,IPO组、ISO组和EPO组IS/AAR及血清CK、LDH活性均明显降低(P<0.05);与EPO组比较,EPO+GLI组、EPO+5-HD组IS/AAR明显增加,血清CK、LDH活性明显升高(P<0.05)。结论乳化异氟醚可模拟缺血后处理减轻兔在体心肌缺血/再灌注损伤,这种心肌保护作用可能与线粒体KATP通道的激活有关。

Aim To investigate the cardioprotective effects and the role of mitochondrial ATP sensitive potassium channel in emulsified isoflurane postconditioning against ischemia reperfusion injury in rabbits. Methods Seventy-six male New Zealand white rabbits underwent 30 min ischemia followed by 180 min reperfusion and were randomly divided into 10 groups：Control group （ CON, n = 8 ）, Ischemia postconditioning group （ IPO, n = 8 ） , 1.0 MAC Isoflurane postconditioning group （ ISO, n = 8） , 1.0 MAC Emulsified isoflurane postconditioning group （ EPO, n = 8 ）, Intralipid group （ INT, n = 7 ） , Glibenclamide group （ GLI, a nonselective ATP sensitive potassium channel inhibitor, 0. 3 mg · kg ^- 1, n = 7 ） , 5-hydroxydecanoate group （5-HD, a selective mitochondrial ATP sensitive potassium channel inhibitor, 5mg · kg ^- 1, n = 8 ）, 0.3 mg · kg ^- 1 GLI ＋ 1.0 MAC EPO group （ GLI ＋ EPO, n = 8） , 5 mg · kg ^- 1 5-HD ＋ 1.0 MAC EPO group （5-HD ＋EPO, n = 7 ） , Dimethylsulfoxide group （ DMSO, the vehicle for GLI, n = 7 ）. Infarct size （IS） and a percentage of the area at risk （AAR） were determined by 2,3,5- triphenyhetrazolium （ TFC ） staining; Serum CK and LDH activities were measured after 180 min reperfu- sion. Results Compared with CON group, the IS/ AAR and serum CK, LDH activities of IPO and EPO groups were declined significantly （ P 〈 0.05 ）. Compared with EPO group, the IS/AAR and serum CK, LDH activities of GLI ＋ EPO and 5-HD ＋ EPO groups were raised significantly （ P 〈 0.05 ）. Conclusion Mitochondrial KATP channel activation is involved in the protective effects of emulsified isoflurane postconditioning against myocardial ischemia repeffusion injury in rabbits.