多巴胺D1,D2受体激动剂对脑缺血/再灌注损伤的影响

目的 研究多巴胺D1,D2受体激动剂对沙土鼠前脑缺血/再灌注（I/R）海马CA1区神经元凋亡及动物行为学的影响.方法 采用沙土鼠前脑I/R模型,缺血时间5 min.动物分为假手术组、I/R组、SKF-38393组、培高利特组.分别于再灌注1天、3天及7天行开阔法行为学和组织病理学观察以及原位末端标记（TUNEL）法检查CA1区神经元凋亡.结果 行为学检查结果显示,I/R组再灌注各时间点沙土鼠探索活动较假手术组明显活跃（P〈0.05）,培高利特组探索活动较I/R组明显减少（P〈0.05）;病理学及TUNEL结果显示, 培高利特组再灌注3天及7天海马CA1区存活锥体细胞较I/R组增多（P〈0.01）,凋亡细胞较I/R组减少（P〈0.05）.预先应用SKF-38393对以上结果无明显影响.结论 多巴胺D2受体激动剂培高利特能减轻脑I/R海马神经元凋亡及动物行为学异常.

Effects of D1 and D2 dopamine receptor agonists on cerebral ischemia/reperfusion injury

Objective To investigate the effects of stimulating D_1 and D_2 dopamine receptors on neuronal apoptosis in hippocampal CA1 area and behavior following forebrain ischemia in gerbils.?Methods The ischemia was induced by occlusion of the two common carotid arteries for 5 min.The animals were randomly assigned to shamoperation group,ischemia/reperfusion(I/R) group,D_1 dopamine receptor agonist SKF-38393 group,and D_2 dopamine receptor agonist pergolide group.The open field test,H-E staining and TUNEL staining were carried out 1,3 and 7 days after reperfusion.?Results The open field test showed that the behavior was significantly impaired(gaining higher activity scores) in the I/R group,compared to the sham-operation group;and the exploring activity of gerbils in the pergolide group was less than that in the I/R group.Histopathology on the 3rd and 7th days revealed there were more survival neurons in the hippocampal CA1 area in the pergolide group than in the I/R group.TUNEL staining on the 3rd and 7th days revealed the apoptotic neurons in the hippocampal CA1 area were less in the pergolide group than in the I/R group.Pretreatment with D_1 receptor agonist SKF38393 had no such effects on the transient I/R injury model.?Conclusion Activation of the D_2 dopamine receptors with pergolide will attenuate the neuronal apoptosis in hippocampal CA1 area and improve the behavioral deficiency in gerbils after transient forebrain ischemia.