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目的:探讨硫辛酸(LA)对帕金森病(PD)模型大鼠黑质内星形胶质细胞胶质纤维酸性蛋白(GFAP)、小胶质细胞离子钙接头蛋白(Iba-l)、酪氨酸羟化酶(TH)表达的影响。方法:130只雄性SD大鼠随机分为对照组(颅内注射生理盐水)30只、模型组(颅内注射6-OHDA)100只。30只对照组大鼠术后4周再随机取20只作为假手术组;100只模型组大鼠4周后随机取80只成功模型再随机分为PD模型组和硫辛酸干预低、中、高剂量组,每组20只。模型组采用立体定位仪定向注射6-OHDA。对照组定向注射等体积的生理盐水。硫辛酸低、中、高剂量组于PD模型大鼠成功术后4周分别每日腹腔注射15、30、60 mg/kg,连续注射14 d。干预结束后取各组大鼠右侧中脑黑质采用Western Blot方法检测GFAP和Iba-l的表达,采用免疫组化方法检测黑质内TH的表达情况。结果:(1)与假手术组比较,PD模型组及硫辛酸干预低、中、高剂量组大鼠黑质内GFAP及Iba-1的表达均明显有所增加(P<0.05),但TH阳性细胞数则明显有所减少(P<0.01);(2)与PD模型组比较,硫辛酸干预低、中、高剂量组大鼠黑质内GFAP及Iba-1表达均明显减少(P<0.05),而TH阳性细胞数则明显增加(P<0.05);(3)与硫辛酸干预低剂量组比较,硫辛酸干预中、高剂量组大鼠黑质内GFAP及Iba-1表达均明显减少(P<0.05),而TH阳性细胞数则明显有所增加(P<0.01);(4)硫辛酸干预中、高剂量组间大鼠黑质内GFAP及Iba-1的表达虽无显著差异(P>0.05),但TH阳性细胞数则明显有所增加(P<0.05)。结论:硫辛酸通过抑制帕金森病模型大鼠黑质内星形胶质细胞和小胶质细胞的过度表达,保护多巴胺能神经元,该结果可为帕金森病的治疗提供新的思路。
Objective: To investigate the effects of lipoic acid (LA) on glial fibrillary acidic protein (GFAP), microglial ionocalculin (Iba-1), asparagus in the substantia nigra of Parkinson’s disease (PD) Effect of Hydroxylase (TH) Expression. Methods: Thirty male Sprague Dawley rats were randomly divided into control group (intracranial injection of normal saline) 30 and model group (intracranial injection of 6-OHDA). Thirty rabbits in the control group were randomly selected as the sham-operated group four weeks after the operation. Totally 80 rats were randomly divided into PD model group and lipoic acid intervention group, High-dose group, each group of 20. Model group using stereotactic directional injection of 6-OHDA. The control group was injected with equal volume of normal saline. Lipoic acid in the low, middle and high dose groups were injected intraperitoneally with 15, 30 and 60 mg / kg 4 weeks after the successful PD model rats, respectively, for 14 days. After the intervention, the right middle cerebral substantia nigra of each group was taken to detect the expression of GFAP and Iba-1 by Western Blot. The expression of TH in substantia nigra was detected by immunohistochemistry. Results: (1) Compared with the sham operation group, the expression of GFAP and Iba-1 in substantia nigra of PD model group and lipoic acid intervention group were significantly increased (P <0.05), but TH (2) Compared with PD model group, the expression of GFAP and Iba-1 in substantia nigra of low, medium and high dose lipoic acid intervention groups were significantly decreased (P < 0.05), while the number of TH positive cells increased significantly (P <0.05). (3) Compared with low-dose lipoic acid intervention group, the expression of GFAP and Iba-1 in substantia nigra was significantly increased (P <0.01). (4) The inhibitory effect of lipoic acid on the expression of GFAP and Iba-1 in the substantia nigra of middle and high dose groups was not significant (P <0.05), while the number of TH positive cells was significantly increased (P> 0.05), but the number of TH positive cells increased obviously (P <0.05). Conclusion: Lipoic acid can protect dopaminergic neurons by inhibiting the overexpression of astrocytes and microglia in the substantia nigra of Parkinson’s disease rats. This result may provide a new idea for the treatment of Parkinson’s disease.