脑纹状体多巴胺系统在急性CO中毒后的变化研究

Study on the dynamic changes of the dopamine system in the striatum of rats after acute carbon monoxide poisoning

目的观察急性一氧化碳(CO)中毒后纹状体多巴胺(DA)及其代谢产物含量的动态变化,探讨单胺氧化酶B(MAO-B)及DA系统变化在急性CO中毒迟发性脑病(delayed neruopsychologic sequelae,DNS)发病中的意义。方法采用腹腔注射CO法制备急性CO中毒大鼠模型,利用阿朴吗啡诱导旋转实验鉴定DNS模型,分析不同模型脑组织纹状体DA系统、MAO-B活性变化。结果急性CO中毒后纹状体MAO-B活性即明显降低,仅为对照组水平的43%;同时用清醒动物脑微透析实验观察纹状体DA及其代谢产物浓度变化发现,CO中毒后1 h DA浓度即增加,其代谢产物则明显降低,提示急性CO中毒早期DA代谢显著降低;中毒14 d后DNS模型大鼠纹状体MAO-B活性显著增加,为对照组活性的1.7倍,DA浓度则显著降低,仅为对照组的29%,代谢产物浓度明显增加,提示出现运动功能障碍的DNS模型脑纹状体MAO-B活性显著升高,DA代谢明显增加。结论急性CO中毒DNS大鼠脑纹状体MAO-B活性可异常升高,加速DA代谢,影响DA神经系统保持锥体及锥体外系运动协调功能,同时生成的大量DA代谢产物具有毒性作用,可进一步加重脑循环障碍和氧化应激损伤,形成恶性循环。

Objective To study on the changes of monoamine oxidase B（MAO-B）,dopamine（DA）and its metabolites dihydroxyphenylacetic acid（DOPAC）and homovanillic acid（HVA）in the striatum of free-moving rats after carbon monoxide（CO）poisoning.Methods Experimental animal groups were as follows：（1）Control group,（2）CO exposure with 1 h group,（3）Delayed neuropsychologic sequelae（DNS）group and（4）non-DNS group.CO was injected into rats intra-peritoneally at a dosage of 120 ml/kg for the first time,and repeated injection of CO（60 ml/kg）was subsequently provided for 3 times at 4 h intervals.We measured HbCO levels in the blood of rats for 24 hours after the first CO administration,and observed the changes of DA and its metabolites＇ levels in the striatum in these groups,as determined by means of brain microdialysis.Results There was significant change with the activity of MAO-B and DA level in DNS model after carbon monoxide poisoning.In the forepart period after CO poisoning,the activity of MAO-B was decreased significantly and the metabolism of DA was decreased remarkably too,but at the time that occurred DNS generally,the unusual elevation was found in the DNS group,and the metabolism of DA was increased significantly.Conclusion These data suggested that the dysfunction of corticospinal and extracorticospinal tract might be relation to the disorder of DA system in the striatum,and the metabolites of DA could further aggravate the cerebral circulation dysfunction and the oxidative damage,resulting in a vicious circle.