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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(P<0.05),中脑ATP水平明显降低(P<0.05),膜电位显著降低(P<0.05),TH表达水平显著降低(P<0.05),HSP60表达水平无明显变化(P>0.05);硫辛酸治疗后,治疗组左侧肢体使用次数显著上升(P<0.05),ATP水平显著升高(P<0.05),膜电位显著升高(P<0.05),TH表达水平显著增高(P<0.05),HSP60表达水平略微降低,但无统计学意义(P>0.05)。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。
Objective To investigate the changes of mitochondria and the protective effect of lipoic acid in Parkinson’s disease (PD) rats. Methods Eighty SD male rats were randomly divided into sham operation group (n = 20) and model group (n = 60). The 6-hydroxydopamine (6-OHDA) was injected into the right striatum of rats to establish the PD model. The sham operation group was injected with the same dose of saline. After the fourth week of modeling, the rats were randomly divided into PD group (n = 20) and control group (n = 20). The rats in the treatment group were given lipoic acid 50 mg / kg · d intraperitoneally for 14 d, PD group given the same dose of saline. After 2 weeks of treatment, Cylinder test was used to analyze the motor ability of rats; chemiluminescence was used to detect the ATP level in substantia nigra of right middle cerebral artery; the mitochondrial membrane potential was measured by JC-1 method; Tyrosine hydrogenase (TH) levels; Western blotting detection of HSP60 expression. Results Compared with the sham operation group, the number of left limbs in PD group decreased significantly (P <0.05), the level of ATP in midbrain decreased significantly (P <0.05), the membrane potential decreased significantly (P <0.05), and the expression of TH decreased significantly (P <0.05), and there was no significant change in the expression of HSP60 (P> 0.05). After treatment with lipoic acid, the number of left limbs in treatment group increased significantly (P <0.05) (P <0.05). The expression of TH was significantly increased (P <0.05), and the expression of HSP60 was slightly decreased (P <0.05). Conclusions The mitochondrial function of substantia nigra in PD rats is decreased but the number of mitochondria is not significantly changed. Lipoic acid can significantly improve the symptoms and mitochondrial function of PD.