锰卟啉络合物对MPTP诱导的帕金森病小鼠的防治作用(英文)

Catalytic metalloporphyrin protects against MPTP-induced Parkinson's disease in mice

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),MnT-DM+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(malon-dialdehyde,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。

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-phenyl- 1, 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.