2,5-己二酮对大鼠脊髓组织蛋白激酶含量的影响  

Effects of 2,5-hexanedione on Protein Kinase Contents in Rats Spinal Cord

作　　者：王青山[1] 侯丽艳[1] 张翠丽[1] 宋福永[1] 朱振平[1] 谢克勤[1] 

机构地区：[1]山东大学公共卫生学院卫生毒理学研究所,山东济南250012

出　　处：《环境与健康杂志》2008年第5期391-395,共5页Journal of Environment and Health

基　　金：国家973课题基金资助项目(2002CB512907);国家自然科学基金资助项目(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)对2,5-己二酮(HD)中毒性周围神经病神经丝(NF)变化的作用。方法将30只体重为200～240g的SPF级雄性Wistar大鼠随机分为3组(1个对照组、2个染毒组),每组10只。经腹腔染毒HD,剂量分别为200和400mg/kg,每周染毒5d,每日1次,连续8周,建立HD中毒性神经病模型。对照组给予相同体积的生理盐水。利用SDS-PAGE和Western Blotting方法检测脊髓胞浆蛋白和膜蛋白组分中PKA、PKC、p35前体和CDK5的相对含量。结果在脊髓胞浆蛋白组分中,与对照组比较,PKA和PKC含量在400mg/kg染毒组大鼠分别升高了46.1%和23.0%(P<0.01),而在200mg/kg染毒组均无明显改变(P>0.05);p35前体和CDK5在200mg/kg染毒组分别升高了56.8%(P<0.01)和78.2%(P<0.01),而在400mg/kg染毒组,仅CDK5升高了21.9%(P<0.01),p35前体含量无明显改变。在脊髓膜蛋白组分中,PKA和CDK5含量在200、400mg/kg染毒组大鼠分别升高了19.3%(P<0.01),25.5%(P<0.01)和26.3%(P<0.01),12.7%(P<0.01);PKC含量仅在400mg/kg染毒组升高了13.9%(P<0.01),而在200mg/kg染毒组无明显改变(P>0.05);染毒组p35前体与对照组比较,变化不明显(P>0.05)。结论HD使脊髓组织中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 （CDKS） in the alterations of neurofialments （NFs） in 2, 5-hexanedione （HD） induced toxic peripheral neuropathies. Methods HD was administrated to male Wistar rats by intraperitoneal injection at doses of 200 or 400 mg/kg, once a day, for 8 consecutive weeks. The relative contents of PKA, PKC, p35 precursor and CDK5 in spinal cord were determined by using SDS-PAGE and Western Blotting. Results In the cytosolic fraction of spinal cord, the levels of PKA and PKC in 400 mg/kg group significantly increased （P〈0.01） by 46.1% and 23.0%, respectively, p35 precursor and CDK5 significantly increased （P〈0.05） by 56.8% and 78.2% respectively in the 200 mg/kg group, while CDK5 increased by 21.9% in the 400 mg/kg group. In the membrane fraction of spinal cord, PKA and CDK5 levels in both the 200 and 400 mg/kg HD-treated rats increased significantly （P〈0.01） by 19.3%, 25.5% and 26.3%, 12.7%, respectively. The content of PKC increased by 13.9% （P〈0.01） in the 400 mg/kg group rats, while p35 precursor levels unchanged. Conclusion HD can increase the contents of PKA, PKC and CDK5 in the spinal cords of rats, which may be one of the toxic mechanisms of HD-induced peripheral neuropathies.

关 键 词：环境污染物 2 5-己二酮 中毒性神经病 蛋白激酶 磷酸化 

分 类 号：R996.4[医药卫生—毒理学]