利多卡因减轻异氟醚对Fischer344老年大鼠海马神经元线粒体的损伤  

Lidocaine reduces mitochondria damage induced by isoflurane in hippocampus of old rats

作　　者：杨尚泽 李瑾[1] 朱晓秋[1] 徐辉[1] 郭明炎[1] 杨斌[2] 林道炜[1] 

机构地区：[1]中山大学孙选仙纪念医院麻醉科,广州510120 [2]中山大学孙选仙纪念医院胃肠外科,广州510120

出　　处：《中华实验外科杂志》2017年第1期72-74,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金青年基金（81201022）;广东省医学科学技术研究基金（A2012188）

摘　　要：目的观察利多卡因对异氟醚处理后的Fischer344老年大鼠海马神经元线粒体损伤的保护作用并探讨其作用机制。方法将18个月Fischer344老年大鼠分为3组（6只/组）：对照组、异氟醚组、异氟醚＋利多卡因组。原位缺口末端标记法（TUNEL）法检测大鼠海马神经元凋亡，Western blot检测半胱氨酰天冬氨酸特异性蛋白酶（Caspase）-3及H4细胞中B细胞淋巴瘤/白血病-2相关X蛋白（bax）/B细胞淋巴瘤/白血病-2（bcl-2）的表达，电镜观察线粒体形态，线粒体膜电位检测试剂盒（JC-1）法检测线粒体膜电位变化，检测线粒体呼吸链复合酶活性变化。结果异氟醚处理Fischer344老年大鼠后，其神经元明显染成褐色，且细胞凋亡因子Caspase-3的表达明显升高（0.30±0.09）%；线粒体明显膨胀、基质密度降低及线粒体嵴断裂；而异氟醚＋利多卡因组中线粒体的这些改变明显减少。异氟醚组线粒体膜电位去极化比例[（85.9±3.5）%]明显高于对照组[（14.1±4.8）%]，而异氟醚＋利多卡因组的比例明显降低[（52.5±5.9）%]。异氟醚组线粒体复合酶Ⅳ的活性明显降低，异氟醚＋利多卡因组的活性明显升高。H4细胞实验中异氟醚＋利多卡因组bax/bcl-2的比率[（0.6±0.2）%]明显低于异氟醚组[（2.4±0.9）%]。结论异氟醚可导致Fischer344老年大鼠海马神经元线粒体形态及功能损伤，进而导致细胞凋亡，而利多卡因可减轻异氟醚对线粒体的损伤产生细胞保护作用。Objective To research the protective effect of lidocaine on mitochondria damage caused by isoflurane in hippocampus of old rats.Methods The 18-month-old Fisher 344 rats were divided into 3 groups （6 rats per group）： control group, 1.2% isoflurane group and 1.2% isoflurane ＋ lidocaine group. The apoptosis was examined through TdT-mediated dUTP nick end labeling （TUNEL）, the expression of cysteinyl aspartate-specific protease （Caspase）-3 and B cell lymphoma/leukemia-2 associated X protein （bax）/B cell lymphoma/leukemia-2 （bcl-2） was detected by Western blotting, and mitochondria morphological characteristics were observed through electron microscope. The activity of mitochondrial respiratory chain and the mitochondrial membrane potential were tested.Results By comparison with control group, isoflurane could not only increase apoptosis rate, but also increase the expression of Caspase-3 [（0.11±0.04）% vs. （0.30±0.09）%] and bax/bcl-2 [（0.6±0.2）% vs. （2.4±0.9）%]. However lidocaine reduced the expression of Caspase-3 and bax/bcl-2. As compared with control group, isoflurane depressed the activity of mitochondrial respiratory chain and the mitochondrial membrane potential [（14.1±4.8）% vs. （85.9±3.5）%]. After adding lidocaine, the activity and potential were elevated to （52.5±5.9）%.Conclusion Lidocaine could relieve the neurotoxicity of isoflurane though reducing mitochondria damage in hippocampus of old rats.

关 键 词：利多卡因 异氟醚 线粒体 海马神经元 脱噬作用 

分 类 号：R614[医药卫生—麻醉学]