培高利特对沙土鼠前脑缺血再灌注损伤的保护作用

Protective effects of pergolide on forebrain ischemia-reperfusion injury in gerbils

目的 研究培高利特 (Pergolide)对沙土鼠前脑缺血再灌注损伤的影响。方法 采用双侧颈总动脉阻断法制作沙土鼠前脑缺血再灌注损伤模型 ,缺血 5min。实验分假手术 (Sham)组、脑缺血再灌注 (I-R)组、培高利特 (I -PER)组。用高效液相色谱 -电化学检测法测定纹状体多巴胺 (DA)、3,4 -双羟苯乙酸 (DOPAC)和高香草酸 (HVA)的含量 ,并计算多巴胺代谢率 ([DOPAC +HVA]/DA) ,以水杨酸捕捉法测定海马 2 ,3-二羟基苯甲酸 (2 ,3-DHBA)含量反映羟自由基 (·OH)的含量。再灌注后第 7天行海马CA1区锥体细胞形态学检查。结果 再灌注 6 0min时I-R组纹状体多巴胺含量明显低于Sham组 (P <0 0 1 ) ,多巴胺代谢率明显高于Sham组 (P <0 0 1 ) ,I-PER组纹状体多巴胺代谢率明显低于I-R组 (P <0 0 5 ) ;I-R组海马2 ,3-DHBA含量明显高于Sham组 (P <0 0 1 ) ,I -PER组海马 2 ,3-DHBA含量明显低于I-R组 (P <0 0 5 ) ;I-R组再灌注第 7天海马CA1区锥体细胞数为Sham组的 7 8% ,I-PER组海马CA1区形态正常锥体细胞数明显多于I-R组。结论 培高利特可抑制脑缺血再灌注期间纹状体多巴胺的释放和代谢 ,减少再灌注期间海马·OH含量 。

Objective To investigate the effect of pergolide on forebrain ischemia-reperfusion injury in gerbils. The extent of injury was assessed by histological and biochemical endpoints.Methods Forebrain ischemia-reperfusion in gerbils was produced by occlusion of bilateral carotid arteries for 5 minutes.Gerbils were randomly divided into 3 groups:Sham-operated (Sham)group;Forebrain ischemia-reperfusion(I-R) group;Pergolide(I-PER) group.Tissue contents of dopamine(DA),dilidroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in striatum and the contents of hydroxyl free radical(·OH) in Hippocampus were measured with high performance liquid chromatography-electroc-hemical detection (HPLC-ECD).DA turnover ratio (/DA) was calculated.At 7th day after ischemia Hippocampal CA1 region was used to carry out the histological evaluation.Results Compared with Sham group,striatum DA contents in I-R group decreased 25 2% (P<0 01),and DA turnover ratio in that group increased 67 1% (P<0 01) respectively at 60 minutes after reperfusion.DA turnover ratio in I-PER group decreased 18 0% (P<0 05) compared with I-R group;Compared with Sham group,Hippocampal 2,3-DHBA contents in I-R group increased 121 7% (P<0 01). Compared with I-R group,Hippocampal 2,3-DHBA contents in I-PER group decreased 29 4% (P<0 05);In I-R group,the number of remaining viable-looking neurons in Hippocampal CA1 region was 7 8% of Sham group and was much less than that in I-PER group (P<0 01).Conclusion Pergolide has neuroprotective effects by attenuating ischemia-reperfusion induced increase of DA metabolism in striatum and the increase of Hippocampal·OH contents.