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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 investigate the effect of manganese (Ⅲ) meso-tetrakis (N, N’-diethylimidazolium-2-yl) porphyrin and MnTDM on the synthesis of 1-methyl- 6-tetrahydropyridine (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -induced model of early Parkinson’s disease in mice, and explore its possible mechanism. Methods: Male C57BL / 6 mice were randomly divided into MPTP model group (subcutaneous injection of 25 mg / kg MPTP for 3 days), MnT-DM + MPTP group (subcutaneous injection of 15 mg / kg MnTDM 1 h before MPTP injection) Control group, saline control group, 10 rats in each group. Behavioral tests such as climbing pole and swimming were performed on the third day after the last injection. The levels of dopamine (DA) and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) and (HVA). Thiobarbituric acid (TBA) method was used to determine the level of malondialdehyde (MDA) in striatum of mice in each group. Results: Compared with the control group, MPTP group significantly reduced the levels of DA, DOPAC and HVA in striatum (P <0.01) and the levels of MDA in mice with acute Parkinson’s disease (P < 0.05); but short-term behavioral indicators of mice have little effect. MnTDM could partially inhibit the above-mentioned effects of MPTP. Compared with MPTP group, the levels of DA, DOPAC and HVA in striatum and the levels of MDA in MnTDM + MPTP group were significantly decreased (all P <0.05). There was no significant difference in behavioral indexes among the mice in each group. CONCLUSION: MnTDM can inhibit lipid peroxidation and promote the secretion of dopamine neurotransmitter, and has some preventive and therapeutic effects on MPTP-induced Parkinson’s disease in mice.