DDAH/NOS途径参与甲基苯丙胺大鼠纹状体的神经毒性研究
Involvement of DDAH/NOS pathway in methamphetamine-induced neurotoxicity in rat striatum
作者：宋健文;刘增甲;谭晓辉;吴雨虹;王慧君;
Author：
收稿日期： 年卷（期）页码：2010,25(06):-679-681
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：甲基苯丙胺;神经毒性;二甲基精氨酸二甲基氨基水解酶;一氧化氮合酶;细胞凋亡
Key words：
基金项目：国家自然科学基金资助项目(批准号:30872918)
中文摘要
目的探讨二甲基精氨酸二甲基氨基水解酶(DDAH)/一氧化氮合酶(NOS)途径在甲基苯丙胺(METH)神经毒性中发挥的作用及其相关调控机制。方法将20只♂Wistar大鼠,随机分为NS对照组和METH组,分别ip生理盐水或METH15mg.kg-1,bid,用药4 d。采用HE染色光镜观察大鼠脑组织的病理学改变,Western蛋白印迹法检测大鼠纹状体区的DDAH1蛋白表达水平,以紫外分光光度计检测NOS的活性。结果 METH组大鼠脑组织中出现神经元水肿和明显的噬神经细胞现象,与NS组相比,METH组大鼠纹状体区的DDAH 1蛋白表达水平显著性升高(P
参考文献
[1]Deng X,Wang Y,Chou J,et al.Methamphetamine causes wide-spread apoptosis in the mouse brain:evidence from using an im-proved TUNEL histochemical method[J].Brain Res Mol BrainRes,2001,93:64-69.
[2]Cadet JL,Jayanthi S,Deng X.Speed kills:cellular and molecularbases of methamphetamine-induced nerve terminal degenerationand neuronal apoptosis[J].Faseb J,2003,17:1775-1788.
[3]李艳红,王慧君,乔东访.甲基苯丙胺对大鼠纹状体小胶质细胞及NOS的影响[J].南方医科大学学报,2008,28(10):1789-1791.
[4]Vallance P,Leone A,Calver A,et al.Accumulation of an endoge-nous inhibitor of nitric oxide synthesis in chronic renal failure[J].Lancet,1992,339:572-575.
[5]McDermott.Studies on the catabolism of NG-methylarginine,NG,NG-dimethylarginine and NG,NG-dimethylarginine inthe rabbit[J].Biochem J,1976,154:179-184.
[6]Lin KY,Ito A,Asagami T,et al.Impaired nitric oxide synthasepathway in diabetes mellitus:role of asymmetric dimethylarginineand dimethylarginine dimethylaminohydrolase[J].Circulation,2002,106:987-992.
[7]Abe T,Tohgi H,Murata T,et al.Reduction in asymmetrical dim-ethylarginine,an endogenous nitric oxide synthase inhibitor,inthe cerebrospinal fluid during aging and in patients with Alzhei-mer’s disease[J].Neuroscience Letters,2001,312:177-179.
[8]Cho AK,Melega WP,Kuczenski R,et al.Relevance of pharmaco-kinetic parameters in animal models of methamphetamine abuse[J].Synapse,2001,39:161-166.
[9]宋健文,刘增甲,谭晓辉,等.N-乙酰半胱氨酸减轻大鼠纹状体甲基苯丙胺神经毒性[J].中国药理学通报,2009,25(6):765-769.
[10]李学锋,邱平明,金贺,等.甲基苯丙胺对相关脑区的神经毒性作用[J].解剖学杂志,2007,30(1):63-65.
[11]Murray-Rust J,Leiper J,McAlister M,et al.Structural insightsinto the hydrolysis of cellular nitric oxide synthase inhibitors bydimethylarginine dimethylaminohydrolase[J].Nat Struct Biol,2001,8:679-683.
[12]Ogawa T,Kimoto M,Sasaoka K.Occurrence of a newenzyme cat-alyzing the direct conversion of NG,NG-dimethyl-L-arginineto L-citrulline in rats[J].Biochem Biophys Res Commun,1987,148:671-677.
[13]Leiper J,Vallance P.Biological significance of endogenous methy-larginines that inhibit nitric oxide synthases[J].Cardiovasc Res,1999,15,43(3):542-548.
【关闭】
