2,5-己二酮中毒大鼠坐骨神经中PKA、PKC和CDK5含量的变化  

The changes of PKA,PKC and CDK5 contents in sciatic nerve of 2,5-hexanedione-intoxicated rats

作　　者：王青山[1] 侯丽艳[1] 张翠丽[1] 宋福永[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,山东济南250012

出　　处：《毒理学杂志》2008年第3期184-187,共4页Journal of Toxicology

基　　金：国家973课题基金资助(2002CB512907);国家自然科学基金课题资助(30271138)

摘　　要：目的探讨蛋白激酶A(PKA),蛋白激酶C(PKC)和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。方法雄性Wistar大鼠200、400 mg/kg HD腹腔注射染毒,每周5次,连续8周,建立HD中毒性神经病模型。利用SDS-PAGE和Western Blotting方法检测坐骨神经胞浆和膜组分中PKA、PKC、p35前体、p35、p25和CDK5的相对含量。结果PKA、PKC、p35前体、p25和CDK5含量在200和400 mg/kg染毒组大鼠坐骨神经胞浆蛋白组分中均呈明显升高,与对照组相比差异有统计学意义(P<0.05);PKC、p35前体和p35在胞膜蛋白组分中变化趋势与胞浆蛋白中相似,也明显升高,并且与对照组相比差异亦有统计学意义(P<0.05),但PKA、CDK5在坐骨神经胞膜蛋白组分中未能检出。结论坐骨神经中PKA、PKC和CDK5含量明显升高,提示相关蛋白激酶含量的升高可能是HD致中毒性周围神经病的发病机制之一。Objective To clarify the role of protein kinase A（PKA）,protein kinase C（PKC） and cyclin dependent kinase5（CDK5） in 2,5-hexanedione（HD） induced toxic peripheral neuropathies.Methods Male Wistar rats were administrated HD at dosage of 200 or 400 mg/kg for 8 weeks（five-times per week）.The contents of PKA,PKC,p35 precursor,p35,p25 and CDK5 in sciatic nerve were analyzed by Western blotting.Results In the cytosolic fraction of sciatic nerve,the levels of PKA,PKC,p35 precursor、p25 and CDK5 significantly increased（P〈0.01） in both the 200 and 400 mg/kg group rats compared to those of control rats.PKC、p35 precurosr and p35 showed the same pattern and increased significantly（P〈0.01） in the membrane fration of sciatic nerve of both HD-intoxicated rats.However,the PKA and CDK5 had not been detected in the present experimental condition.Conclusion HD could elevate the contents of PKA,PKC and CDK5 in sciatic nerve of rats,which may be one of the toxic mechanism of HD-induced toxic peripheral neuropathies.

关 键 词：2 5-己二酮 蛋白激酶 磷酸化 坐骨神经 

分 类 号：R99[医药卫生—毒理学]