CAJ | 학술논문

目的:观察锰卟啉络合物[manganese(Ⅲ)meso-tetrakis(N,N'-diethylimidazolium-2-yl) porphyrin,MnTDM]对1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)诱导的早期帕金森病模型小鼠的防治效果,探讨其可能的作用机制.方法:C57BL/6雄性小鼠随机分为MPTP模型组(连续3 d皮下注射25 mg/kg MPTP),MnTDM+MPTP组(于MPTP注射前1 h皮下注射15 mg/kg MnTDM)以及MnTDM对照组、生理盐水对照组,每组10只.末次注射后第3日进行爬杆和游泳等行为学检测;HPLC-ECD法检测各组小鼠纹状体多巴胺(dopamine,DA)及其代谢产物3,4-二羟基苯乙酸(DOPAC)和高香草酸(HVA)水平;硫代巴比妥酸(thiobarbituric acid,TBA)法测定各组小鼠纹状体丙二醛(malondialdehyde,MDA)水平.结果:急性注射MPTP可建立早期帕金森病小鼠模型;与对照组相比,MPTP组小鼠纹状体DA、DOPAC、HVA水平明显下降(P＜0.01),MDA水平明显升高(P＜0.05);但短期对小鼠行为学指标影响不大.MnTDM能部分抑制MPTP的上述作用;与MPTP组相比,MnTDM+MPTP组小鼠纹状体DA、DOPAC、HVA水平明显上升,MDA水平明显下降(P均＜0.05).各组小鼠间行为学指标无统计学差异.结论:MnTDM能抑制脂质过氧化,促进多巴胺类神经递质分泌,对MPTP诱导的帕金森病小鼠有一定防治作用.
목적:관찰맹계람락합물[manganese(Ⅲ)meso-tetrakis(N,N'-diethylimidazolium-2-yl) porphyrin,MnTDM]대1-갑기-4-분기-1,2,3,6-사경필정(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)유도적조기파금삼병모형소서적방치효과,탐토기가능적작용궤제.방법:C57BL/6웅성소서수궤분위MPTP모형조(련속3 d피하주사25 mg/kg MPTP),MnTDM+MPTP조(우MPTP주사전1 h피하주사15 mg/kg MnTDM)이급MnTDM대조조、생리염수대조조,매조10지.말차주사후제3일진행파간화유영등행위학검측;HPLC-ECD법검측각조소서문상체다파알(dopamine,DA)급기대사산물3,4-이간기분을산(DOPAC)화고향초산(HVA)수평;류대파비타산(thiobarbituric acid,TBA)법측정각조소서문상체병이철(malondialdehyde,MDA)수평.결과:급성주사MPTP가건립조기파금삼병소서모형;여대조조상비,MPTP조소서문상체DA、DOPAC、HVA수평명현하강(P＜0.01),MDA수평명현승고(P＜0.05);단단기대소서행위학지표영향불대.MnTDM능부분억제MPTP적상술작용;여MPTP조상비,MnTDM+MPTP조소서문상체DA、DOPAC、HVA수평명현상승,MDA수평명현하강(P균＜0.05).각조소서간행위학지표무통계학차이.결론:MnTDM능억제지질과양화,촉진다파알류신경체질분비,대MPTP유도적파금삼병소서유일정방치작용.
Objective: To observe the effects of manganese( Ⅲ ) meso-tetrakis (N, N'-diethylimidazolium-2-yl) porphyrin (MnTDM) in treatment of early Parkinson's disease(PD) mouse model induced by subcutaneous injection of 1-methyl-4-phenyl1, 2, 3, 6-tetrahydropyridine(MPTP) and to discuss its possible mechanism. Methods:Forty male C57BL/6 mice were evenly randomized into 4 groups: MPTP model group(subcutaneous injection of 25 mg/kg MPTP for 3 days), MnTDM+ MPTP group (15 mg/kg MnTDM was subcutaneously injected 1 h before MPTP injection), MnTDM control group, and normal saline group. Performance of animals in the pole and swimming test was observed 3 days after the last injection. Levels of dopamine (DA) and its metabolites(3,4-dihydroxyphenylacetic acid [DOPAC] and homovanillic acid [HVA]) in the striatum of animals were measured by high-performance liquid chromatography with an electrochemical detector(HPLC-ECD). Thiobarbituric acid (TBA) method was used to examine the levels of malondialdehyde(MDA). Results: Acute injection of MPTP could be used for establishment of PD model. The striatal levels of DA, DOPAC and HVA in MPTP group were significantly lower(P＜0.01)and the striatal level of MDA was significantly higher(P＜0.05) than those of the control group. MPTP had no obvious effect on the behavioral performance of the animals in a short term. MnTDM could partly inhibit the above effects of MPTP. Compared with MPTP group, MnTDM+ MPTP group had significantly higher DA, DOPAC, and HVA levels and significantly lower MDA level(all P＜0.05). There was no significant difference in the behavioral indices of animals between the 4 groups. Conclusion:MnTDM can inhibit lipid peroxidation and promote DA production; it has preventive and therapeutic effects on MPTP induced PD.