摘要：

目的 探讨京尼平苷对1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）诱导帕金森病模型小鼠的神经保护作用及其可能作用机制。方法 共48 只雄性C57BL/6小鼠，随机分为正常对照组（对照组）、帕金森病模型组（模型组）、京尼平苷组和MPTP + 京尼平苷组，自主活动计数观察小鼠行为学变化，免疫组织化学染色观察中脑黑质酪氨酸羟化酶（TH）和Bcl-2 阳性细胞数目，原位末端标记法检测中脑黑质神经元凋亡情况。结果 与对照组相比，模型组小鼠移动格子数［（76.33 ± 8.59）次/5 min 对（142.50 ± 11.65）次/ 5 min，P = 0.000］、站立次数［（19.58 ± 3.97）次/5 min 对（39.17 ± 4.75）次/5 min，P = 0.000］、TH 阳性细胞数目［（12.83 ± 2.32）个/高倍视野对（35.67 ± 1.75）个/高倍视野，P = 0.000］和Bcl-2 阳性细胞数目［（10.83 ± 2.23）个/高倍视野对（20.67 ± 1.75）个/高倍视野，P = 0.000］减少，凋亡细胞数目增加［（20.33 ± 2.58）个/高倍视野对（3.83 ± 1.67）个/高倍视野，P = 0.000］；经京尼平苷治疗后，MPTP + 京尼平苷组小鼠移动格子数［（97.67 ± 13.15）次/5 min，P = 0.000］、站立次数［（29.33 ± 2.90）次/5 min，P = 0.000］、TH 阳性细胞数目［（17.50 ± 2.07）个/高倍视野，P = 0.002］和Bcl-2 阳性细胞数目［（15.17 ± 2.79）个/高倍视野，P = 0.003］增加，凋亡细胞数目减少［（14.67 ± 3.08）个/高倍视野，P = 0.001］。结论 京尼平苷对MPTP 诱导的帕金森病模型小鼠中脑黑质多巴胺能神经元具有保护作用，其作用机制可能与京尼平苷抑制神经元凋亡有关。

关键词: 帕金森病, 环烯醚萜类, 细胞凋亡, 疾病模型, 动物

Abstract:

Objective  To investigate the neuroprotective effect of geniposide on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) induced Parkinson's disease (PD) model mice and possible mechanism.  Methods  A total of 48 male C57BL/6 mice were randomly divided into control, model, geniposide and MPTP + geniposide groups. The behaviors of C57BL/6 mice were assessed by using open field test, the tyrosine hydroxylase (TH) and Bcl-2 positive neurons in the midbrain substantia nigra of mice were detected by immunohistochemistry and the number of apoptosis neurons were observed with TdT-mediated dUTP-biotin nick end labeling (TUNEL).  Results  The number of mobile grid [(76.33 ± 8.59) times/5 min], standing [(19.58 ± 3.97) times/5 min], TH-positive neurons [(12.83 ± 2.32)/HPF] and Bcl-2-positive neurons [(10.83 ± 2.23)/HPF] in model group were significantly lower than those in the control group [(142.50 ± 11.65) times/5 min, (39.17 ± 4.75) times/5 min, (35.67 ± 1.75)/HPF, (20.67 ± 1.75)/HPF; P = 0.000, for all]. The apoptosis neurons in model group [(20.33 ± 2.58)/HPF] were significantly higher than that in control group [(3.83 ± 1.67) /HPF, P = 0.000). The number of mobile grid [(97.67 ± 13.15) times/5 min, P = 0.000], standing [(29.33 ± 2.90) times/5 min, P = 0.000], TH-positive neurons [(17.50 ± 2.07)/HPF, P = 0.002] and Bcl-2-positive neurons [(15.17 ± 2.79) /HPF, P = 0.003] in MPTP + geniposide group were significantly higher than those in model group. The number of apoptosis neurons [(14.67 ± 3.08) /HPF] in MPTP + geniposide group was significantly lower than that in model group (P = 0.001). Conclusions Geniposide can protect dopaminergic neurons in MPTP-induced neurodegeneration and the mechanism may be associated with the inhibition of neuronal apoptosis.

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