3-硝基丙酸预处理对黑质多巴胺神经元能量代谢的影响

目的　观察 3 -硝基丙酸(3- nitropropionic acid,3 NP)预处理对黑质腺苷酸及腺苷含量的影响,探讨能量代谢及腺苷含量改变在3- NP预处理保护多巴胺(dopamine,DA)神经元中的作用。方法　64 只雄性 SD大鼠随机分为对照组、3 -NP组、PD组及3- NP预处理组。3 -NP预处理组于6 羟基多巴胺(6 -OHDA)损毁前 24 h经腹腔注射3 NP (按体重20 mg/kg),采用高效液相色谱法(HPLC)测定术后2 h和1、3、5 d时间点损毁侧黑质腺苷酸及腺苷含量。结果　3- NP组2 h,帕金森病(PD)组3、5 d及3- NP预处理组各时间点较对照组ATP含量明显降低,腺苷酸ADP、-AMP等增高(P<0 .05或P<0. 01),3- NP预处理组3、5 d较PD组同时间点相比ATP水平增高(P<0. 05);3- NP预处理组各时间点腺苷持续在较高水平,与PD组同时间点相比显著增高(P<0 .01)。结论　3 -NP轻度抑制氧化磷酸化使能量代谢水平降低,有利于细胞能量储备和增强对后续抑制的耐受能力。腺苷水平增高在3 NP预处理保护神经元过程中可能具有重要作用。

Effects of 3-nitropropionic Acid Preconditioning on Energy Metabolism of Dopaminergic Neuron within Substantia Nigra

Objective To study the effects of 3-Nitropropionic acid(3-NP) preconditioning(PC) on energy metabolism within substantia nigra(SN) in 6-OHDA-lesioned Pakinson disease(PD) rat model and the role of adenosine in the mechanism of neuroprotection on dopaminergic neurons in SN following chemical PC by 3-NP. Methods The adult rat PD models were established after unilateral stereoscopically microinjection of 6-OHDA into the right side SN pars compacta(SNpc).The rats in the sham-operated (control) group were treated with 0.9% saline by stereoscopical and intraperitoneal (ip) injection, those in the 3-NP group were administered 3-NP (20 mg/kg, ip), those in the PC group received 3-NP (20 mg/kg,ip) 24 h before 6-OHDA-lesioned.At 2 h,1,3,and 5 d after the stereoscopically microinjection, the levels of ATP,ADP,AMP and adenosine in the SN homogenate were detected by high-performance liquid chromatography (HPLC) analysis. Results The content of ATP in the SN at 3,5 d time point in 3-NP PC group is significantly higher than that in PD group(P<005).The level of adenosine increased markedly and remained higher at all time points in 3-NP PC group, and it was statistically significantly higher than that in PC group(P<001). Conclusions The results suggest that mild inhibition of oxidative phosphorylation by PC with 3-NP seems to activate compensatory mechanisms, which prevent further decrease of energy metabolism. The increase of adenosine would play a critical role in the mechanism of protection on DA neurons in SN induced by 3-NP preconditioning.