硫辛酸对帕金森病大鼠黑质线粒体的保护作用
本文选题:帕金森病 + -羟基多巴胺 ; 参考:《山东大学学报(医学版)》2017年08期
【摘要】:目的探讨帕金森病(PD)大鼠模型中脑线粒体的变化及硫辛酸的保护作用。方法 80只SD雄性大鼠,随机分为假手术组(20只)、模型组(60只)。将6-羟基多巴胺(6-OHDA)注入大鼠右侧纹状体建立PD模型,假手术组注入同等剂量的生理盐水。建模第4周后运用旋转实验筛选成功模型(40只),随机分为PD组(20只)、治疗组(20只),治疗组给予硫辛酸50 mg/kg·d腹腔注射,连续14 d,PD组给予同等剂量生理盐水。治疗2周后,Cylinder test分析大鼠运动能力;化学发光法检测大鼠右侧中脑黑质ATP水平;JC-1法检测中脑线粒体膜电位;免疫组化、Western blotting检测各组大鼠酪氨酸氢化酶(TH)水平;Western blotting检测HSP60的表达。结果与假手术组比较,PD组左侧肢体使用次数显著减少(P0.05),中脑ATP水平明显降低(P0.05),膜电位显著降低(P0.05),TH表达水平显著降低(P0.05),HSP60表达水平无明显变化(P0.05);硫辛酸治疗后,治疗组左侧肢体使用次数显著上升(P0.05),ATP水平显著升高(P0.05),膜电位显著升高(P0.05),TH表达水平显著增高(P0.05),HSP60表达水平略微降低,但无统计学意义(P0.05)。结论 PD大鼠黑质线粒体功能降低但线粒体数量无明显改变,硫辛酸可显著改善PD症状及线粒体功能。
[Abstract]:Objective to investigate the changes of cerebral mitochondria and the protective effect of lipoic acid in Parkinson's disease (PD) rat model. Methods 80 SD male rats were randomly divided into sham operation group (n = 20) and model group (n = 60). The PD model was established by injecting 6-hydroxydopamine 6-OHDAs into the right striatum of rats, and the sham operation group was injected with the same dose of normal saline. After 4 weeks of modeling, 40 successful models were selected by rotating experiment, and were randomly divided into PD group (n = 20) and treatment group (n = 20). The treatment group was intraperitoneally injected with lipoic acid for 50 mg/kg d and the PD group was given the same dose of normal saline for 14 days. After 2 weeks of treatment, the motor ability of rats was determined by Cylinder test, the ATP level in the right midbrain of rats was detected by chemiluminescence assay and the mitochondrial membrane potential of mesencephalon was detected by JC-1 method. The expression of HSP60 was detected by Western blotting at the level of tyrosine hydrogenase (THH). Results compared with the sham-operated group, the number of left limb use in PD group was significantly reduced, the level of ATP in midbrain was significantly decreased, the level of membrane potential was significantly decreased, and the expression level of HSP60 was significantly decreased in PD group, while the expression level of HSP60 in P0.05 was not significantly changed after lipoic acid treatment. In the treatment group, the frequency of use of the left limb was significantly increased and the level of P0.05 + ATP was significantly increased. The membrane potential was significantly increased and the expression of P0.05TH was significantly increased. The expression level of HSP60 was slightly decreased, but there was no significant difference between the two groups. Conclusion the mitochondrial function of substantia nigra in PD rats was decreased, but the number of mitochondria was not changed. Lipoic acid could significantly improve the symptoms and mitochondrial function of PD.
【作者单位】: 贵州医科大学人体解剖学教研室;贵州医科大学生物学教研室;贵州医科大学附属医院神经内科;贵州医科大学附属医院儿科;
【基金】:贵州省科技厅联合基金(黔科合LG字[2012]021,黔科合LH字[2014]7077) 贵州省化学合成药物研发利用工程技术研究中心(黔科合[2016]平台人才5402) 贵州省普通高等学校药物化学工程研究中心(黔教合KY字[2014]219号)
【分类号】:R742.5
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