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目的探讨垂体腺苷酸环化酶激活肽27(PACAP27)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(PD)小鼠是否具有治疗作用。方法静脉给予神经肽 PACAF27对 MPTP诱导的 PD 小鼠模型进行治疗,采用免疫组织化学及蛋白印迹分析方法对 PD 标志物酪氨酸羟化酶(TH)、多巴胺转运体(DAT)、囊泡单胺转运体2(VMAT2)进行检测,并用高效液相色谱(HPLC)检测纹状体单胺类递质。结果神经肽 PACAP 可明显减少黑质 TH 阳性细胞的损失,以 PACAP(0.02μg/d)治疗组最为明显(93.33±4.87,F=85.58,P<0.01)。生理盐水(NS)治疗组较正常对照组纹状体 TH、DAT、VMAT 的表达明显降低,而 PACAP 治疗组较 NS 治疗组 TH 表达明显增多,以PACAP 治疗组(0.02μg/d)增高最为明显(136.34±8.45,F=113.88,P<0.01);而 DAT 和 VMAT2在 PACAP 治疗组中则呈现了多种变化趋势。HPLC 检测发现 PACAP 治疗组(0.02μg/d)多巴胺(DA)代谢产物二羟苯乙酸(DOPAC)含量较 NS 治疗组明显升高(1590.7±473.3,F=375.71,P<0.01),与正常对照组差异无统计学意义(P>0.05)。结论静脉注射 PACAP27可对 MPTP 诱导的PD 小鼠模型产生明显的治疗作用,而这种治疗作用可能与单胺类递质转运体 DAT、VMAT2的表达高低无明显直接关系。
Objective To investigate the effect of pituitary adenylate cyclase activating peptide 27 (PACAP27) on Parkinson’s disease (PD) mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Does it have a therapeutic effect? Methods MPTP-induced PD mice were treated by intracerebral administration of neuropeptide PACAF27. Immunohistochemistry and Western blotting were used to evaluate the effects of PD markers tyrosine hydroxylase (TH), dopamine transporter (DAT) Amine transporter 2 (VMAT2) was detected by high performance liquid chromatography (HPLC) detection of monoamine neurotransmitters. Results The neuropeptide PACAP significantly reduced the loss of substantia nigra TH-positive cells. The most obvious was PACAP (0.02μg / d) (93.33 ± 4.87, F = 85.58, P <0.01). Compared with the normal control group, the expression of TH, DAT and VMAT in the NS group was significantly lower than that in the normal control group, while the PAC expression in the PACAP group was significantly higher than that in the NS group (P <0.05). The PACAP treatment group (0.02μg / d) (136.34 ± 8.45, F = 113.88, P <0.01). However, DAT and VMAT2 showed many changes in the PACAP treatment group. The content of DOPAC in PACAP treatment group (0.02μg / d) was significantly higher than that in NS treatment group (1590.7 ± 473.3, F = 375.71, P <0.01) by HPLC. Compared with normal control There was no significant difference between the two groups (P> 0.05). Conclusion Intravenous injection of PACAP27 may have a significant therapeutic effect on MPTP-induced PD mice. However, this therapeutic effect may not be directly related to the expression of monoamine transporters DAT and VMAT2.