Conclusion
METH induces the activation of NOS and increases NO level to cause the occurrence of PDI-SNO, leading subsequently to increased expression of αSN in mouse striatum and hippocampus. L-NNA, the inhibitor of NOS, can partly relieve nervous system toxicity induced by METH. 目的: 研究亚硝基化的二硫键异构酶（PDI）对甲基苯丙胺（METH）致小鼠海马及纹状体区α-突触核蛋白（α-SN）表达的影响。 方法: 利用C57小鼠METH亚急性中毒模型，使用一氧化氮合酶（NOS）抑制剂N-硝基-L-精氨酸（L-NNA）与METH共同造模，实验分为对照组、L-NNA组、METH组、METH+L-NNA组。Western Blotting技术检测各组海马及纹状体区内一氧化氮合酶（NOS）、PDI及其S亚硝基化（PDI-SNO）和α-SN表达情况。一氧化氮试剂盒检测各组一氧化氮含量。 结果: METH给药后NOS、一氧化氮含量、PDI-SNO、α-SN表达较对照组均明显升高（P < 0.05）；L-NNA与METH共处理后与METH组对比，NOS表达下降（P < 0.05），一氧化氮含量明显减少（P < 0.05），能够显著抑制PDI-SNO表达（P < 0.05），伴随α-SN表达降低（P < 0.05）。而MET H+L-NNA组、L-NNA组与对照组比较均无明显差异（P>0.05）。 结论: METH作用后诱导NOS活化，一氧化氮含量升高，PDI发生显著S亚硝基化而功能失活，导致相关脑区α-SN表达升高，而NOS抑制剂L-NNA能部分缓解METH神经毒性作用。
Methods
Forty C57BL/6 mice were randomized equally into saline control group, METH group, L-NNA (a NOS inhibitor) group and L-NNA plus METH group. All the agents were injected intraperitoneally at an interval of 12 h, and a total of 8 injections were administered; in L-NNA plus METH group, METH was injected 30 min after LNNA in each treatment. Western Blotting was used to detect the expression of nitric oxide synthase (NOS), αSN, PDI and Snitrosylation of protein disulphide isomerase (PDI-SNO) in the hippocampus and striatum of the mice, and nitric oxide (NO) levels were determined using a NO assay kit.
Objective
To investigate the role of Snitrosylation of protein disulphide isomerasec in methamphetamine (METH)-induced expression of alpha synuclein (αSN) in mouse hippocampus and striatum neurons.
Results
In METH group, the levels of NOS, PDISNO, αSN and NO all increased significantly compared with those in the control group (P<0.05). Combined treatment with L-NNA and METH, compared with METH alone, resulted in significantly lowered expression of NOS, NO, PDI-SNO and αSN in the hippocampus and striatum of the mice (all P<0.05). No significant differences were found in NOS, NO, PDI-SNO or αSN expressions among METH+L-NNA, L-NNA and control groups (P>0.05).