硫辛酸对帕金森模型大鼠黑质内神经胶质细胞及多巴胺能神经元的影响

The effect of lipoic acid on neuroglial cell and dopaminergic neurons in substantia nigra of Parkinson's disease model rats

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 effect of lipoic acid （LA） on astrocytes glial fiber acid protein （GFAP）, microgliain ionized calcium-blinding adaptor molecule 1 （Iba-1） and tyrosine hydroxylase （TH） in substantia nigra in Parkinson＇s disease （PD） model rats. Methods： 130 male SD rats were randomly divided into control group （30 rats, intracranial injection of saline） and model group （100 rats, intracranial injection of 6-OHDA）. After 4 weeks, 20 of 30 rats in control group were randomly selected as sham operation group, and 80 of the model rats were randomly divided into PD model group and lipoic acid intervention （low, medium and high dose） groups, 20 rats in each group. After 4 weeks injection of lipoic acid, successful model rats were continuous intraperitoneal injection of 15, 30, 60 mg/kg/d for 14 days respectively. After intervention, the expression of GFAP and Iba-1 by Western Blot and the expression of tyrosine hydroxy- lase （TH） by immunohistochemistry were detected at the right substantia nigra of rats. Results： （1） Compared with the sham group, the expression of Iba-1 and GFAP was significantly increased （P 〈 0.05 ）, while the number of TH positive cells was markedly decreased （P 〈0.01 ） in PD model group and lipoic acid in low, medium and high dose group. （2） Compared with the model group, the expression of Iba-1 and GFAP was significantly decreased （ P 〈 0. 05 ） , while the number of TH positive cells was significantly increased （ P 〈 0. 05 ） in lipoic acid group （ low, medium and high）. （ 3 ） Compared with the lipoic acid in low dose group, the expression of Iba-1 and GFAP in lipoic acid in medium and high dose group decreased obviously （ P 〈 O. 05 ）. The number of TH positive cells in lipoic acid in medium and high dose group increased significantly （P 〈 0. O1 ）. （4） Compared to the lipoie acid in medium and high dose group, the expression of Iba-1 and GFAP had no significant difference （P 〉 0.05）, but the number of TH positive cells increased significantly in thelipoic acid in highdose group （P 〈 0.05 ）. Conclusion ： Lipoic acid protects dopaminergic neurons through inhibiting the over-expression of astrocytes and microglia in substantia nigra in Parkinson＇s model rats which provids a new idea for the treatment of Parkinson＇s disease.