Ginkgo biloba affords dose-dependent protection against 6-hydroxydopamine-induced parkinsonism in rats:: neurobehavioural, neurochemical and immunohistochemical evidences
Ginkgo biloba affords dose-dependent protection against 6-hydroxydopamine-induced parkinsonism in rats:: neurobehavioural, neurochemical and immunohistochemical evidences
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DOI：
10.1111/j.1471-4159.2005.03000.x
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发表时间：
2005-04-01
影响因子：
4.7
通讯作者：
Islam, F
中科院分区：
文献类型：
--
作者：
Ahmad, M;Saleem, S;Islam, F
银杏叶提取物（EGB）是一种有效的抗氧化剂和单胺氧化酶B（MAO-B）抑制剂，在6-羟基多巴胺（6-OHDA）帕金森病大鼠模型中评价其抗帕金森病作用。大鼠分别给予50、100和150 mg/kg银杏叶提取物3周。在第21天，将2 μ L 6-OHDA（10 μ g在0.1%抗坏血酸盐水中）注射到右侧纹状体中，而假手术组接受2 μ L载体。注射6-OHDA后三周，测试大鼠的旋转行为、自发活动和肌肉协调。6周后，处死动物以估计硫代巴比妥酸反应物质（TBARS）和还原型谷胱甘肽（GSH）含量的产生，测量谷胱甘肽-S-转移酶（GST）、谷胱甘肽还原酶（GR）、谷胱甘肽过氧化物酶（GPx）、过氧化氢酶和超氧化物歧化酶（SOD）的活性，并定量儿茶酚胺、多巴胺（DA）D2受体结合，和酪氨酸羟化酶免疫反应（TH-IR）纤维密度。药物诱导的旋转增加以及由于6-OHDA注射引起的自发活动和肌肉协调的缺陷被EGb显著且剂量依赖性地恢复。病变后，随着TBARS的产生增加，黑质中GSH含量显著减少，EGb治疗后逐渐恢复。银杏叶提取物还剂量依赖性地恢复谷胱甘肽依赖性酶，过氧化氢酶和SOD的活性，在纹状体中，这已显着降低了损伤。6-OHDA注射后，纹状体DA及其代谢产物水平显著降低，多巴胺能D2受体数量增加，EGb治疗后两者均显著恢复。最后，所有这些结果都表现为EGb治疗后病变组同侧黑质TH-IR纤维密度增加;病变几乎完全丧失TH-IR纤维。考虑到我们的行为学研究，生化分析和免疫组化观察，我们得出结论，银杏叶提取物可作为一种治疗方法，以检查神经元的损失后帕金森氏症。
Ginkgo biloba extract (EGb), a potent antioxidant and monoamine oxidase B (MAO-B) inhibitor, was evaluated for its anti-parkinsonian effects in a 6-hydroxydopamine (6-OHDA) rat model of the disease. Rats were treated with 50, 100, and 150 mg/kg EGb for 3 weeks. On day 21, 2 mu L 6-OHDA (10 mu g in 0.1% ascorbic acid saline) was injected into the right striatum, while the sham-operated group received 2 mu L of vehicle. Three weeks after 6-OHDA injection, rats were tested for rotational behaviour, locomotor activity, and muscular coordination. After 6 weeks, they were killed to estimate the generation of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) content, to measure activities of glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD), and to quantify catecholamines, dopamine (DA) D2 receptor binding, and tyrosine hydroxylase-immunoreactive (TH-IR) fibre density. The increase in drug-induced rotations and deficits in locomotor activity and muscular coordination due to 6-OHDA injections were significantly and dose-dependently restored by EGb. The lesion was followed by an increased generation of TBARS and significant depletion of GSH content in substantia nigra, which was gradually restored with EGb treatment. EGb also dose-dependently restored the activities of glutathione-dependent enzymes, catalase, and SOD in striatum, which had reduced significantly by lesioning. A significant decrease in the level of DA and its metabolites and an increase in the number of dopaminergic D2 receptors in striatum were observed after 6-OHDA injection, both of which were significantly recovered following EGb treatment. Finally, all of these results were exhibited by an increase in the density of TH-IR fibers in the ipsilateral substantia nigra of the lesioned group following treatment with EGb; the lesioning had induced almost a complete loss of TH-IR fibers. Considering our behavioural studies, biochemical analysis, and immunohistochemical observation, we conclude that EGb can be used as a therapeutic approach to check the neuronal loss following parkinsonism.