右美托咪定对布比卡因中毒大鼠心肌细胞线粒体损伤的保护
Protective effects of Dexmedetomidine on the mitochondrial damage of cardiomyocytes in Bupivacaine-induced rats
作者：张静
Author：
收稿日期： 年卷（期）页码：2020,35(05):-496-500
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：右美托咪定;心肌细胞;心律失常;线粒体损伤;布比卡因;AMPK/SIRT1/PGC-1α;能量代谢;氧化应激
Key words：
基金项目：
中文摘要
目的探讨右美托咪定(Dex)是否通过AMPK/SIRT1/PGC-1α信号通路调节布比卡因(BPV)中毒大鼠心肌细胞线粒体的能量代谢和氧化应激。方法将40只大鼠随机均分为空白对照组、模型组及Dex 30、60 min组。空白对照组经静脉持续泵入0.9%生理盐水3 mL·kg~(-1)·min~(-1),20 min后处死;模型组大鼠经静脉持续泵入0.5%BPV 2 mg·kg~(-1)·min~(-1),直至出现心律失常后处死;Dex 30、60 min组大鼠经静脉持续泵入0.5%BPV 2 mg·kg~(-1)·min~(-1),至出现心律失常后,分别持续静脉泵入3μg·kg~(-1)·h~(-1)Dex 30、60 min后处死。检测大鼠线粒体Na~+-K~+-ATP酶、Ca~+-Mg~+-ATP酶、乳酸盐脱氢酶(LDH)、活性氧(ROS)的活性,超氧化物歧化酶(SOD)、丙二醛(MDA)含量及AMPK、SIRT1、PGC-1αmRNA和蛋白表达的变化。结果 Dex可使大鼠心肌细胞线粒体中Ca~(2+)-Mg~(2+)-ATP酶、Na~+-K~+-ATP酶及SOD的活性显著升高,LDH活性及MDA、ROS的水平显著降低,改善线粒体形态结构;同时可上调AMPK、SIRT1和PGC-1αmRNA和蛋白的表达。结论 Dex可减轻BPV的心脏毒性,可能是通过调控AMPK/SIRT1/PGC-1α信号通路来改善线粒体的能量代谢和减轻氧化应激来保护BPV中毒大鼠的心肌线粒体。
参考文献
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