奥沙利铂治疗大鼠坐骨神经线粒体呼吸功能及抗氧化酶活性改变的研究  

Mitochondrial dysfunction and decrease of antioxidase activities are involved in oxaliplation chemotherapy-induced peripheral neuropathy

作　　者：刘国凯[1,2] Gary Bennett 

机构地区：[1]北京中医药大学东直门医院麻醉科,北京100700 [2]加拿大麦吉尔(McGill)大学麻醉科及疼痛中心

出　　处：《中国临床药理学与治疗学》2012年第3期289-293,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：目的:观察奥沙利铂治疗大鼠坐骨神经线粒体呼吸功能的改变及抗氧化酶活性的变化。方法:选取SD雄性大鼠36只,用5%葡萄糖将奥沙利铂溶液稀释到2mg/mL,连续5d(d 0～d 4)腹腔注射2mg/kg;对照组大鼠接受对照液5%葡萄糖注射。并于d 0、d 8、d 15、d 22、d 29、d 35及d 41测定机械异常痛敏(4g VFH)和机械痛敏(15g VFH)。取d 27～d 35并确认存在异常痛敏和机械痛敏的大鼠及对照组大鼠各9只,处死大鼠并取坐骨神经,将神经制作成切碎的纤维细丝(M&T)标本,将标本放入呼吸测定仪里,分别加入底物并测定呼吸比率变化;再取模型和对照组大鼠各9只,取坐骨神经并提取线粒体,分别测定抗氧化酶硫氧还原蛋白还原酶(TrR)和谷胱甘肽过氧化物酶(GPx)的活性。结果:与对照组大鼠比较,注射奥沙利铂大鼠在疼痛高峰期(d 27～d 35)呼吸比率明显下降(下降16%),奥沙利铂治疗大鼠线粒体加入细胞色素C后呼吸明显增加;而且TrR(下降23%)和GPx(下降15.4%)的活性明显下降。结论:奥沙利铂治疗大鼠坐骨神经线粒体功能受损,引起线粒体呼吸功能失调,预示损伤存在于复合物I或复合物II;抗氧化酶活性下降可能是线粒体呼吸功能降低的另一个原因。To measure and evaluate the function on mitochondrial respiration and antiox- idase activities of sciatic nerves in rats of oxali- plation-induced peripheral neuropathy. METH- ODS： 36 adult male Sprague-Dawley rats （150- 200 g） were housed on sawdust bedding in plas-tic cages. A stock solution of oxaliplatin was di- luted to 2 mg/mL with 5 % dextrose in distilled water and injected IP at 2 mg/kg on five consec- utive days （d 0-d 4） in a volume of 1.0 mL/kg. Control animals were received vehicle （5% dextrose） injections. All respirometricalstudies described below use animals with con- firmed oxaliplatin-evoked neuropathic pain. Mechano-allodynia and mechano-hyperalgesia were assessed on d 8, d 22, d 27, d 35, and d41 postoperatively. The sciatic nerves of 9 model and 9 vehicle rats were excised on d 27-35 post- operatively. The nerves were minced into seg- ments about lmm long. Each segment was then teased apart into microfilaments （the mince ＆ tease （M7T） preparation）. We assessed mito- ehondrial activity consists of the sequential addi- tion of substrates and inhibitors for the several complexes of the electron transport system （ETS; a more accurate term than ＂ electron transport chain＂）. The sciatic nerves of 9 model rats on d7 and d35 and 9 vehicle rats were used to assay GPx and TrR activity. RESULTS. We found that peripheral nerve mitochondria from oxaliplatin-treated rats had significantly lower respiratory control ratios. The vehicle-treated vs. oxaliplatin-treated differences in these two ratios were about 16% We also found that the addition of cytochrome C had no effect on respi- ration in the control animals （the normal result） but significantly increased respiration in the ox- aliplatin-treated animals. The data also sugges- ted that oxaliplatin treatment caused a signifi-cant decrease （15.4%） in the activity of a key anti-oxidant enzyme, glutathione peroxidase （GPx）. Moreover, we had found a significant decrease （23~） in the activity of another key anti

关 键 词：化学治疗 奥沙利铂 呼吸比率 疼痛 

分 类 号：R614[医药卫生—麻醉学]