大鼠烯丙基氯染毒对神经纤维微管及其调节因子影响的研究  

The effects of chloropropene on neurofilament microtubule and its modulators in rats

作　　者：孙克任[1] 谢克勤[1] 张磊[1] 张耽 于丽华[1] 

机构地区：[1]山东医科大学毒理学省级重点实验室

出　　处：《卫生毒理学杂志》1997年第4期284-289,共6页Journal of Health Toxicology

摘　　要：本实验研究了大鼠烯丙基氯（ＣＰ）染毒神经纤维微管（ＭＴ）形态、单位面积内数量及其调节因子Ｃａ２＋、ＣａＭ、ｃＡＭＰ、ｃＧＭＰ含量；ＮＦ－ｍｙｏｓｉｎＡＴＰａｓｅ活性；以及ＣＰ和Ｃａ２＋对离体管蛋白组装的影响。结果发现，神经纤维ＭＴ变性、单位面积内ＭＴ数量减少或消失，具有时间效应关系；Ｃａ２＋增加、ＣａＭ减少、ｃＡＭＰ增加、ｃＧＭＰ减少、ｃＡＭＰ／ｃＧＭＰ比值增加，均有剂量效应关系；ＮＦ－ｍｙｏｓｉｎＡＴＰａｓｅ活性降低并有剂量效应关系；ＣＰ和Ｃａ２＋对离体管蛋白组装ＭＴ均有抑制作用并显现良好的剂量效应关系，但Ｃａ２＋在较低浓度（０．１２５ｍｍｏｌ／Ｌ）下即可抑制ＭＴ组装，而ＣＰ在较高浓度（０．１６３ｍｏｌ／Ｌ以上）时方能抑制ＭＴ组装。可以认为，ＣＰ抑制ＭＴ组装或促进ＭＴ去组装可能主要是通过使轴浆内Ｃａ２＋浓度增加所致。轴浆内Ｃａ２＋浓度增加与ＣａＭ结合成Ｃａ２＋－ＣａＭ复合物，一方面活化ＡＣ催化ＡＴＰ生成ｃＡＭＰ，再激活ＰＫＡ；另一方面活化ＣａＭ－ＰＫⅡ，活化的ＰＫＡ及ＣａＭ－ＰＫⅡ催化ＭＡＰ２磷酸化，抑制ＭＴ组装和促进ＭＴ去组装，造成ＭＴ变性和单位面积内数量减少或消失，以及ＮＦ－ｍｙｏｓｉｎＡＴＰａｓｅ活?In this paper effects of Chloropropene (CP) on morphosis and quantity per area of neurofilament and its modulators(intracellular Ca 2+ , CaM,cAMP and cGMP contents, NF myosin ATPase activity) in rats and effects of CP and Ca 2+ on the microtubule(MT) assembly in vitro were studied. The results showed that the neurofilmental MT were denaturated, the quantity of MT per acre were decreased even disappeared with time effect relationship, contents of Ca 2+ percentage, cAMP and the ratio of cAMP to cGMP were increased significantly, however, contents of CaM and cGMP was markedly decreased with dose effect relationship in rats intoxicated with CP, and that microtubule assembly in vitro was inhibited by CP and Ca 2+ with obvious dose effect relationship. These results suggested that inhibition of MT assembly and promotion of MT disassembly might be related to the increase of Ca 2+ in nerve axon. The increase of intracellular Ca 2+ and the Ca 2+ CaM complex activate AC which catalyses ATP to produce cAMP and activates PKA and CaM PKⅡ. Activated PKA and CaM PKⅡ resulted in MAP 2 phosphorylations, the assembly of microtubule inhibition. The decreased assembly and degeneration of microtubules, decreased quantity per area and decreased NF myosin ATPase activity inhibited the transportation in nerve axon. \ \

关 键 词：烯丙基氯 微管 调节因子 大鼠 周围神经 

分 类 号：R992[医药卫生—毒理学]