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药物干预对6-羟基多巴胺处理后大鼠多巴胺神经元、多巴胺及其代谢产物的影响
Effects of Medicine on Dopamine Neurons and DA in Rats Injected with 6-OHDA
【摘要】 目的:研究古拉定、川芎嗪、丹参对6-羟基多巴胺(OHDA)处理后大鼠的黑质多巴胺(DA)神经元及纹状体细胞外液DA的影响。方法;将6-OHDA注射入大鼠黑质,饲养2周后用阿朴吗啡(APO)诱发其旋转行为并计数,饲养2个月时利用微透析法采集大鼠纹状体细胞外液,然后大鼠灌注取脑,酪氨酸羟化酶(TH)单抗染色,观察正常对照组、单纯手术组、古拉定治疗组(古拉定12mg/kg腹腔注射每天1次,共14天)、川芎嗪治疗组(川芎嗪50mg/kg腹腔注射每天1次,共14天)、丹参治疗组(丹参2.5ml/kg腹腔注射每天1次,共14天)的黑质DA神经元的变化,用高效液相色谱电化学法检测细胞外液的DA及代谢产物的含量变化。结果:TH单抗免疫组化染色可见4个手术组的黑质DA神经元计数明显低于正常对照组,差异有极显著性(P<0.001),而4组组间无统计差异;4个手术组纹状体DA的含量低于对照组,差异有显著性(P<0.001),4组的二羟苯乙酸(DOPAC)/DA低于对照组(P<0.001),4组组间均无差异。结论:古拉定、川芎嗪、丹参不能阻止6-OHDA对黑质DA神经元的毒性作用,亦不能增加损伤侧纹状体的DA含量。
【Abstract】 Objective:To study the effect of glutathione (GSH),Ligustrazine and Salvia miltiorrhiza on dopamine (DA) and its metabolites of corpus striatum and DA neurons in rats injected with 6-OHDA. Methods: All the experimental rats were randomly divided into 5 groups. To investigate control rats,6-OHDA-injecting rats without treatment,and 6-OHDA-injecting rats treated with GSH [12 mg/(kg·d) ip 14 d], Ligustrazine [ 50 mg/(kg·d), ip 14 d] or Salvia miltiorrhiza [ 2.5 ml/(kg· d), ip 14 d]. Hydroxydopamine(12 g/L) was injected into right SN of rats through two sites at day 0. Two weeks later, rotationary behaviour was induced by APO on all rats and recorded. In day 60,the extracelluar fluid in CS was collected by microdialysis. Extracellular DA and its metabolites(DOPAC,HVA) in corpus striatum of all groups were measured by high performance liquid chromatography with electrochemical detection (HPLC-ECD) and then the brain of rats in each group was dissociated, the slice was stained with monoclonal anti-hydroxytyro-sinase antibody to examine the alteration of DN in SN in every group by immunohistochemistry. Results: In the control, extracellular DA and DOPAC were significantly higher than those of other groups (P<0.001 ).But there are no differences among 6-OHDA-injecting rats in other groups.The sum of DA neurons in control group is much higher than other groups (P<0.001).There were no significant differences in the sum of DA neurons among other 4 groups. Conclusion: GSH,Ligustrazine, Salvia neither prevent the toxic effect of 6-OHDA in DA neuron nor increase the level of extracellular DA in CS.
【Key words】 Parkinson’s disease; 6-OHDA; dopamine; glutathione; ligustrazine; salvia; rats;
- 【文献出处】 南京医科大学学报(自然科学版) ,Acta Academiae Medicinae Nanjing , 编辑部邮箱 ,2003年05期
- 【分类号】R742.5
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