细胞周期依赖性蛋白激酶5／p35在2，5-己二酮中毒大鼠神经组织中的表达  

Expression changes of cyclin dependent kinase 5/p35 in nerve tissues of 2,5-hexanedione intoxicated rats

作　　者：王青山[1] 侯丽艳[1] 张翠丽[1] 曾涛[1] 杨曦伟[1] 谢克勤[1] 

机构地区：[1]山东大学公共卫生学院毒理学研究所,济南250012

出　　处：《中华劳动卫生职业病杂志》2008年第6期336-340,共5页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：国家“973”课题基金资助（2002CB512907）

摘　　要：目的探讨细胞周期依赖性蛋白激酶5（CDK5）在2，5-己二酮（HD）中毒性周围神经病发病过程中的作用。方法30只雄性Wistar大鼠，随即分为对照组、200mg／kg HD染毒组和400mg／kg HD染毒组，每组10只。染毒途径为腹腔注射，每周5次，连续8周，建立HD中毒性神经病模型。利用Western blotting方法检测大脑、脊髓和坐骨神经胞浆蛋白和膜蛋白中CDK5、p35和p25的相对含量。结果与对照组相比，P35蛋白含量在200、400mg／kg HD染毒大鼠大脑和脊髓胞浆蛋白组分中明显降低，而在脊髓和坐骨神经膜蛋白组分中含量明显升高，差异均有统计学意义（P〈0．01）；p25变化趋势与p35基本一致。CDK5在200、400mg／kg HD染毒大鼠大脑胞浆和膜蛋白中均明显下降；除坐骨神经膜蛋白组分中未检出外，在脊髓和坐骨神经中CDK5含量明显升高，与对照组比较，差异有统计学意义（P〈0．01）。结论HD中毒后大鼠神经组织中CDK5及其激活因子p35和p25发生明显改变，这种改变可能与HD中毒性周围神经病的发病机制有关。Objective To explore the role of cyclin dependent kinase 5 （CDK5） in 2,5-hexanedione （HD）-induced neuropathy. Methods Thirty male Wistar rats weighted 200-240 g were divided randomly into three groups,i.e, control group,200 mg/kg HD group and 400 mg/kg HD group （n=10 for each group）. HD was administered to rats by intraperitoneal injection at dosage of 200 or 400 mg/kg for 8 weeks （five times per week） to establish the intoxicated rats model. The relative contents of CDK5, p35 and p25 were determined in cerebrum, spinal cord and sciatic nerve of rats by Western Blotting. Results Compared with that of the control group rats,p35 contents were significantly decreased （P〈0.01） in the cytosolic fractions of cerebrum and spinal cord in both the 200 and 400 mg/kg HD intoxicated rats, while in the membrane fractions of spinal cord and sciatic nerve,p35 contents were increased significantly（P〈0.01 ）. The changes of p25 showed the same pattern with p35. P25 contents were significantly reduced （P〈0.05） in the cytosolic （cerebrum and spinal cord） and membrane（cerebrum） fractions of both HD-treated rats and were elevated（P〈0.01 ） in the membrane fraction of spinal cord and cytosolic fraction of sciatic nerve. The relative amounts of CDK5 were significantly decreased （P〈0.01） in the cytosolic and membrane fractions of cerebrum in both the 200 and 400 mg/kg HD intoxicated rats. Except for membrane fraction of sciatic nerve ,the significant increased （P〈0.01） of CDK5 were observed in the spinal cord and sciatic nerve of both the 200 and 400 mg/kg HD treated rats. Conclusion HD can induce significant changes of CDK5 and its activators p35,p25 in nerve tissues,which may be related to the neuropathy induced by HD.

关 键 词：己烷类 细胞周期蛋白质依赖激酶类 神经组织 

分 类 号：R114[医药卫生—卫生毒理学]