天麻对帕金森病大鼠黑质凋亡细胞表达及酪氨酸羟化酶阳性神经元的影响

The effect of gastrodin on expression of apoptosis and Tyrosine hydroxylase neurons in substantia nigra pars compacta in rats of Parkinson＇ s disease

目的研究和探讨帕金森病（PD）的发病机理及天麻防治PD的作用机制。方法采用6-羟基多巴胺（6-OHDA）大鼠模型，通过免疫组化技术观察天麻对PD大鼠黑质酪氮酸羟化酶阳性（TH^＋）神经元及Caspase-3阳性（Caspase-3^＋）神经元表达水平的影响。结果PD大鼠脑组织黑质致密部（SNpc）及腹侧被盖区（VTA）TH^＋神经元表达水平组间比较差异有统计学意义（F值分别为13．29、5．04，P〈0．01）。与正常组大鼠脑组织SNpc和VTA区TH^＋神经元表达水平[（32．13±4．84），（30．23±3．21）]比较，模型组大鼠TH^＋神经元表达水平[（18．89±3．73）和（24．20±6．35）]明显下降（P〈0．01）；经天麻和美多巴治疗后TH^＋神经元丢失减少，天麻小剂量组TH^＋神经元表达水平分别为（26．24±3．06）和（26．31±6．1），中剂量组分别为（22．44±3．81）和（26．91±6．28）；大剂量绀分别为（20．95±4．71）和（27．3±7．1）；美多巴组分别为（27．89±4．56）和（25．974±5．14）；其中，天麻小剂量组和美多巴组SNpc区TH^＋神经元表达水平和模型组比较差异有统计学意义（P〈0．05）。PD大鼠脑组织SNpc及VTA区Caspase-3阳性细胞表达水平组间比较差异有统计学意义（F值分别为6．09、5．53，P〈0．01）。与正常组Caspase-3阳性细胞表达水平[（9．83±3．03），（7．04±1．76）]比较，模型组火鼠Caspase-3阳性细胞表达水平[（14．53±2．33）和（12．84±2．58）]明显升高（P〈0．01）；经天麻和美多巴治疗后Caspase-3阳性细胞表达水平下降，天麻小剂量组分别为（10．68±1．83）和（7．72±1．92），中剂量组分别为（11．29±2．8）和（10．38±3．79）；大剂量组分别为（11．89±2．97）和（11．37±1．86）；美多巴组分别为（9．99±3．3）和（10．69±3．11）；其中，美多巴组SNpc区和天麻小剂量组VTA区Caspase-3阳性细胞表达水平和模型组比较差异有统计学意义（P〈0．05）。天麻和美多巴治疗各组TH^＋神经元表达与Caspase-3^＋神经元表达呈相反趋势。结论细胞凋亡可能是PD大鼠中腑多巴胺神经元丢失的主要方式。天麻可通过调节Caspase-3减少细胞凋亡，其中，小剂量天麻对治疗PD具有较好的作用。本研究结果提示天麻可不同程度地保护多巴胺神经元。

Objective To investigate the etiopathogenesls of Parkinson＇ s disease （ PD ） and the mechanism of action of the gastrodin in order to prevent and cure PD. Methods Male Wistar rats were left-striatum injected with 6-OHDA （20 μg） to establish PD model. To ohserve the effect of gastrodin on the expression of Tyrosine hydroxylase positive （ TH^＋ ） and Caspase-3 positive （ Caspase-3^＋ ） neurons in substantia nigra pars compacta （SNpe） and ventral tegmental area （VTA） by immunohistoehemistry technique. Results There were statistically significant differences in the levels of TH^＋ neurons in SNpe and VTA in rats of PD disease between groups （F = 13.29, 5.04,P 〈0.01 ）. To compared with normal group [ （32.13±4.84）, （30.23±3.21 ）], the levels of TH^＋ neurons in SNpc and VTA in rats in model group （ 18.89 ± 3.73,24. 20 ± 6.35 ） were significantly decreased （ P 〈 0.01 ）, the loss of TH^＋ neurons declined after treatment with gastrodin or madopar, the levels of TH^＋ neurons in SNpc and VTA in rats in small dose group [ （26.24 ±3.06） , （26.31 ± 6. 1 ） ] , in middle dose group [ （22.4 ± 3.81 ） , （26.91±6.28）] , in large dose group [（20.95 ±4.71）,（27.3 ±7. 1）1 and in madopar group [（27.89 ± 4. 56） , （25.97± 5.14） ] were obviously increased, the levels of TH ＋ neurons in SNpc in rats in small dose group and in madopar group were significantly increased （ P 〈 0.05 ）. There were statistically significant differences in the levels of Caspase-3^＋ neurons in SNpc and VTA of rats of PD disease between groups （ F =6.09,5.53 ,P 〈0.01 ）. To compared with normal group [ （9.83 ± 3.03 ）, （7.04 ± 1.76） ], the levels of Caspase-3^＋ neurons in SNpc and VTA in rats in model group [ （ 14.53 ± 2.33 ）, （ 12.84 ± 2.58 ）] were significantly increased （ P 〈 0.01 ）, the levels of Caspase-3^＋ neurons in SNpc and VTA in rats in small dose group [ （ 10.68 ± 1.83 ） , （7.72 ± 1.92） ] , in middle dose group [（11.29±2.8）,（10.38±3.79）],inlarge dose group （11.89＋2.97）,（11.37＋1.86）] and in madopar group [ （9.99 ＋ 3.3 ）, （ 10.69 -＋ 3. 11 ） ] were obviously decreased, the levels of Caspase-3 ＋ neurons in SNpe in madopar group and in VTA in small dose group were significantly decreased （ P 〈 0.05 ）. The trend of change of TH ＋ neurons is opposite to that of Caspase-3^＋ neurons in gastrodin or madopar treatment groups. Conclusion Gastrodin may suppress the loss and apoptosis in SNpc by adjusting Caspase-3. The effect of small dose group is better,suggesting gastrodin can have different neuroprotection on dopamine neuron.