Wang C, Hu S M, Xie H, Qiao S G, Liu H, Liu C F
Department of Anesthesiology and Critical Care, The Second Affiliate Hospital, Soochow University, Suzhou, China.
Institute of Neuroscience, Soochow University, Suzhou, China.
Braz J Med Biol Res. 2015 Jun;48(6):528-36. doi: 10.1590/1414-431X20143876. Epub 2015 Mar 27.
This study aimed to determine the role of mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channels and protein kinase C (PKC)-ε in the delayed protective effects of sevoflurane preconditioning using Langendorff isolated heart perfusion models. Fifty-four isolated perfused rat hearts were randomly divided into 6 groups (n=9). The rats were exposed for 60 min to 2.5% sevoflurane (the second window of protection group, SWOP group) or 33% oxygen inhalation (I/R group) 24 h before coronary occlusion. The control group (CON) and the sevoflurane group (SEVO) group were exposed to 33% oxygen and 2.5% sevoflurane for 60 min, respectively, without coronary occlusion. The mitoKATP channel inhibitor 5-hydroxydecanoate (5-HD) was given 30 min before sevoflurane preconditioning (5-HD+SWOP group). Cardiac function indices, infarct sizes, serum cardiac troponin I (cTnI) concentrations, and the expression levels of phosphorylated PKC-ε (p-PKC-ε) and caspase-8 were measured. Cardiac function was unchanged, p-PKC-ε expression was upregulated, caspase-8 expression was downregulated, cTnI concentrations were decreased, and the infarcts were significantly smaller (P<0.05) in the SWOP group compared with the I/R group. Cardiac function was worse, p-PKC-ε expression was downregulated, caspase-8 expression was upregulated, cTnI concentration was increased and infarcts were larger in the 5-HD+SWOP group (P<0.05) compared with the SWOP group. The results suggest that mitoKATP channels are involved in the myocardial protective effects of sevoflurane in preconditioning against I/R injury, by regulating PKC-ε phosphorylation before ischemia, and by downregulating caspase-8 during reperfusion.
本研究旨在利用Langendorff离体心脏灌注模型，确定线粒体三磷酸腺苷敏感性钾（mitoKATP）通道和蛋白激酶C（PKC）-ε在七氟醚预处理延迟性保护作用中的作用。将54只离体灌注大鼠心脏随机分为6组（n = 9）。在冠状动脉闭塞前24小时，将大鼠暴露于2.5%七氟醚60分钟（保护第二窗组，SWOP组）或吸入33%氧气（I/R组）。对照组（CON）和七氟醚组（SEVO）分别在无冠状动脉闭塞的情况下，暴露于33%氧气和2.5%七氟醚60分钟。在七氟醚预处理前30分钟给予mitoKATP通道抑制剂5-羟基癸酸（5-HD）（5-HD + SWOP组）。测量心功能指标、梗死面积、血清心肌肌钙蛋白I（cTnI）浓度以及磷酸化PKC-ε（p-PKC-ε）和半胱天冬酶-8的表达水平。与I/R组相比，SWOP组心功能未改变，p-PKC-ε表达上调，半胱天冬酶-8表达下调，cTnI浓度降低，梗死面积显著减小（P<0.05）。与SWOP组相比，5-HD + SWOP组心功能较差，p-PKC-ε表达下调，半胱天冬酶-8表达上调，cTnI浓度升高，梗死面积更大（P<0.05）。结果表明，mitoKATP通道通过在缺血前调节PKC-ε磷酸化以及在再灌注期间下调半胱天冬酶-8，参与七氟醚预处理对心肌缺血/再灌注损伤的保护作用。
