蛋白酶抑制因子对大鼠帕金森病造模条件探讨
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1.广西中医药大学第一附属医院,南宁 530022;2.广西中医药大学,南宁 530007

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R-33

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Exploration of the conditions for establishing proteasome inhibitor I-induced mouse model of Parkinson’s disease
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1.the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine,Nanning 530022, China. 2. Guangxi University of Traditional Chinese Medicine, Nanning 530007

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    摘要:

    目的 观察不同剂量蛋白酶抑制因子(proteasome inhibitors I,PSI)对大鼠行为学及脑黑质酪氨酸羟化酶(tyrosine hydroxylase,TH)、α-突触核蛋白(α-synuclein,α-syn)表达的影响,探讨 PSI 致帕金森病(Parkinson’ s disease,PD)大鼠慢性模型的最佳条件。 方法 将 30 只 SPF 级雄性大鼠随机分为 3 组,每组 10 只,皮下注射 PSI, 给药剂量分别为模型组 A 3 mg / kg、模型组 B 6 mg / kg,对照组以相同方法注射二甲基亚砜( dimethyl sulfoxide, DMSO)溶液,剂量为 3 mg / kg。 连续隔日(每周一、三、五)注射 2 周后,观察 PD 大鼠的行为学变化,同时常规 HE 染色,在光学显微镜下观察中脑黑质区细胞变化情况,Western blot 及免疫组化染色法检测各组大鼠的脑内多巴胺能神经元黑质酪氨酸羟化酶(TH)、中脑黑质区 α-syn 的表达变化。 结果 与对照组相比,PSI 模型组两组大鼠运动能力明显下降,模型组 A 爬杆实验行为学评分低模型组 B,悬挂实验行为学评分高于模型组 B(P<0.05);HE 染色结果显示:模型组大鼠中脑黑质细胞变性;Western blot 法及免疫组化结果显示:大鼠均出现黑质 TH 表达明显降低、α-syn 的表达显著增加。 结论 PSI 大鼠模型可以复制 PD 的行为学和中枢、外周神经退行性改变特征,是研究 PD 发病机制的有效模型。

    Abstract:

    Objective To observe the effects of different doses of protease inhibitor I (PSI) on behavior and the expression of tyrosine hydroxylase ( TH) and α-synuclein in the substantia nigra of rats, and to explore the optimal conditions for establishing a chronic Parkinson’s disease (PD) rat model induced by PSI. Methods Thirty SPF male rats were randomly and equally divided into three groups. Model groups were subcutaneously injected with PSI at a dose of 3 or 6 mg / kg, while the control group was injected with dimethyl sulfoxide solution at a dose of 3 mg / kg. After injection every other day (every Monday, Wednesday and Friday) for 2 weeks, the behavioral changes of PD rats were observed, and the changes of cells in the substantia nigra of the midbrain were observed by routine HE staining. The expression of TH and α- syn in the substantia nigra of dopaminergic neurons was determined by western blotting and immunohistochemical staining. Results Compared with that in the control group, the motor ability of the rats in the PSI model group was significantly decreased, the behavioral score in the pole climbing test was lower in the 3 mg / kg dose group than that in the 6 mg / kg dose group, and the behavioral score in the suspension test was higher in the 3 mg / kg dose group than that in the 6 mg / kg dose group. The result of HE staining showed that the substantia nigra cells of the model group were degenerated. The result of Western blot and immunohistochemistry showed that the expression of TH decreased significantly and that of α-syn increased significantly in the substantia nigra of rats. Conclusions The PSI rat model can replicate the behavioral and central and peripheral neurodegenerative changes of PD, making it an effective model to study the pathogenesis of PD.

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胡玉英,韦晓芸,宋 曦,钟 洁,刘永辉,罗荣卿.蛋白酶抑制因子对大鼠帕金森病造模条件探讨[J].中国比较医学杂志,2022,32(5):85~90,120.

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  • 收稿日期:2021-07-27
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  • 在线发布日期: 2022-07-05
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