中文摘要：

目的:研究缺氧时纹状体多巴胺能神经毒性的机制。方法:采用大鼠纹状体脑片体外培养模型,以底物磷酸化³²P-掺入法测定Ca²⁺-钙调蛋白依赖性蛋白激酶Ⅱ（CCDPKⅡ）的活性。结果:缺氧30min,纹状体脑片CCDPKⅡ活性降低75％,慢性利血平化使得缺氧诱导的酶活性降低程度减轻,与对照组相比大约降低40％。外源性多巴胺显著降低纹状体脑片CCDPKⅡ活性。去除胞外Ca²⁺后,多巴胺诱导的酶活性降低作用被削弱。阿扑吗啡（非特异性多巴胺受体激动剂）、SKF38393（特异性D₁样受体激动剂）和喹吡罗（特异性D₂样受体激动剂）均可显著降低CCDPKⅡ的活性。Sch-23390（特异性D₁样受体拮抗剂）和吗丁啉（特异性D₂样受体拮抗剂）均可拮抗多巴胺所诱导的酶活性的抑制作用。结论:多巴胺参与缺氧诱导的纹状体CCDPKⅡ活性抑制,其作用机制与D₁样和D₂样受体的激活以及胞外Ca²⁺的内流有关,从而导致多巴胺介导的纹状体神经损伤。

英文摘要：

AIM: To investigate the mechanism underlying dopa-minergic neurotoxicity in the striatum during anoxia. METHODS: Using rat striatal slices as an in vitro model, the activity of Ca2 + -calmodulin-dependent protein kinase II (CCDPKII) was examined by the method of substrate phosphorylation 32P- incorporation. RESULTS: Anoxia for 30 min greatly reduced CCDPK II activity by about 75 %. Reserpinization by repeated reserpine administration (1 mg·kg-1 ·d-1 for 7 d, sc) preserved CCDPK II activity against the anoxia-induced decrease (about 40 % of control). The activity of CCDPK II was reduced significantly by exposure of rat striatal slices to micromolar concentrations of dopamine in the presence of extracellular Ca2+ . Omission of Ca2+ in the incubation medium (with addition of 1 mmol/L egtazic acid) diminished the dopamine-induced decrease of the kinase activity. Application of apomorphine, a non-selective dopamine receptor agonist, produced a similar concentration-related decrease of CCDPK II activity. Exposure to SKF38393 ( selective D1-like receptor agonist) or quinpirole (selective D2-like receptor agonist) also inhibited the kinase activity. The dopamine-induced decrease of CCDPK II activity was attenuated by preincubation with Sch-23390 (selective D1-like receptor antagonist) or domperidone (selective D2-like receptor antagonist). CONCLUSION: Dopamine is involved in the anoxia-induced inhibition of CCDPK II activity byactivation of both D1-like and D2-like receptors and influx of Ca2+ , which may contribute to dopamine-mediated striatal neuronal damage.