目的 探讨对比1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(PD)小鼠亚急性模型和慢性模型的行为学及组织病理学变化。方法 亚急性模型C57/BL小鼠腹腔注射MPTP 25 mg/kg,每天1次,连续注射7 d;慢性模型C57/BL小鼠腹腔注射MPTP 25 mg/kg,每周注射2次,连续注射5 w。通过爬杆实验和悬挂实验检测小鼠的行为学变化;应用高效液相色谱法检测纹状体内多巴胺(DA)和5-羟色胺(5-HT)的含量;应用免疫组化染色法检测中脑黑质酪氨酸羟化酶(TH)的表达。结果 与对照组相比,慢性组小鼠行为学改变明显,而亚急性组小鼠无明显改变。在爬杆实验中,慢性组小鼠爬杆所用的时间长于亚急性组;悬挂实验中,慢性组小鼠悬挂时间低于亚急性组。两组小鼠纹状体DA含量明显降低(P〈0.05),但慢性组与亚急性组相比DA含量降低程度更明显(P〈0.05);而5-HT含量未见明显改变(P〉0.05);中脑黑质致密部TH阳性细胞减少方面,亚急性组下降至对照组28%,慢性组下降至对照组的17%;慢性组HE染色切片中的神经细胞凋亡最多,而亚急性组神经细胞相对凋亡较少。结论 MPTP的PD小鼠慢性模型与亚急性模型相比,具有更明显的与人类PD相似的临床症状,是以后进一步研究PD病理生理学机制的潜在稳定模型。
Objective To compare behavioral and histopathological changes of subacute and chronic Parkinson disease (PD) mice model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropy ridine(MPTP). Methods Subacute C57/BL mice model was intraperitoneally injected(ip) MPTP 25 mg/kg I time per day for 7 days; chronic C57/BL mice model were intraperitoneally injected(ip) MPTP 25 mg/kg 2 times per week for 5 weeks. The behavioral changes of mice was inspected by climbing pole and suspension test; the content of DA in stratium was detected by HPLC; and the tyrosine hydroxylase (TH) expression in substantia nigra was detected by immunohistochemical staining. Re- suits Compared with that of control group, the behavior of chronic model group was changed significantly. The suspension capability of chro- nic model group was weaker than that of subacute model group in suspension experiment. The content of DA in stratinm of chronic and suba- cute model groups was decreased significantly, and in chronic group, it was significant lower than that of subacute model group ( P〈0.05 ). The amount of TH positive ceils was reduced in the midbrain substantia nigra compacta. Nerve cell apoptosis was most in chronic group and relatively less in subacute group. Conclusions The chronic PD mice model induced by MPTP has more obvious and similar clinical symp- toms and is the potential stability model for further investigating PD pathology physiology mechanism.