摘要
目的探讨神经元型一氧化氮合酶(nNOS)在甲基苯丙胺(METH)所致大鼠中枢神经系统氧化应激损伤中的作用机制。方法建立METH中毒动物模型,并给予nNOS抑制剂7硝基吲唑(7-NI)预处理,观察各组间动物行为学的变化,并检测nNOS表达、多巴胺(DA)含量、硝基化蛋白表达及凋亡等指标。结果 METH组大鼠纹状体中nNOS蛋白表达水平明显升高,而METH+7-NI组nNOS表达水平较METH组明显降低。METH组DA明显降低(P<0.01),而METH+7-NI组、7-NI组与对照组比较,DA无差异(P>0.05)。METH组硝基化蛋白含量明显升高(P<0.01),而METH+7-NI组硝基化蛋白表达较METH组明显降低(P<0.05)。METH组与对照组相比,凋亡细胞数明显升高(P<0.01),而7-NI对凋亡的增高表现出明显的保护作用(与METH组相比P<0.01)。METH组和METH+7-NI组的动物刻板行为评分均明显高于7-NI和对照组(P<0.01),METH、METH+7-NI组间差异无显著性(P>0.05)。结论METH可导致大鼠大脑纹状体nNOS蛋白表达水平增高、DA含量的降低、硝基化蛋白水平升高及细胞凋亡增多等多种神经毒性表现,7-NI能部分减轻其神经毒性作用。METH明显增加大鼠的不自主刻板运动,而应用7-NI预处理后,对刻板行为的改善并不明显。
Aim Tostudytheprotectiveeffectsofin-hibition of neuronal nitric oxide synthase （ nNOS ） in methamphetamine （ METH ） induced neurotoxicity via oxidativestressinjuryinrats.Methods Ratmodelsof acute METH poisoning with/without 7 nitroindazole （7-NI） pretreatment were built to evaluate the protec-tive effects on the changes of ethology, nNOS, nitro-proteins, dopamine （ DA ） and apoptosis in rat stria-tum.Results ThenNOSexpression,nitroproteinex-pression and apoptosis increased significantly in the METH group（ P〈0. 05 ） and 7-NI pretreatment shows a dramatically protective effect against the changes （ P〈0. 05 ） . DA concentration decreased significantly in the METH group（P〈0. 05） and 7-NI pretreatment re-stored the depleted DA to normal level （ P〉0. 05 ） . Stereotyped behavior increased significantly in the METH group and the 7-NI combined group compared with the 7-NI group and the control group（P〈0. 01）. Conclusions 7-NIshowssignificantprotectiveeffects against the alterations of DA level, nNOS expression, nitroprotein expression and apoptosis in rat striatum caused by acute METH poisoning. However, there is no obvious protective effect on METH-induced stereo-typed behavior.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2014年第8期1101-1106,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 81273345)
