Objective

To explore the effects of different doses of dopamine receptor agonist pramipexole on neurobehaviors and changes of mitochondrial membrane potential in rats with global cerebral ischemia-reperfusion injury.

Methods

A total of 75 SPF Sprague-Dawley male rats were randomly divided into sham group (n=20), model group (n=20), pramipexole administration group (n=35). The rat model of global cerebral ischemia-reperfusion injury was prepared by the modified Pulsinelli's four-vessel occlusion method. Pramipexole administration group was administered intraperitoneally in rats with global cerebral ischemia-reperfusion injury at different doses of pramipexole 0.25 mg/kg, 0.5 mg/kg, 1 mg/kg, 2 mg/kg, once a day for 14 consecutive days. Based on the results of modified neurological severity scores, open field test and morphology by Nissl's staining to determine the optimal dose of pramipexole. Mitochondrial membrane potential in the optimal dose of pramipexole administration group were measured by the JC-1 fluorescent probe staining method.

Results

1. Different doses of pramipexole 0.25 mg/kg, 0.5 mg/kg, 1 mg/kg, and 2 mg/kg, were used as drug administration in rats with global cerebral ischemia-reperfusion injury for 14 consecutive days, and we found that all four doses of pramipexole could improve the modified neurological severity scores of rats with global cerebral ischemia-reperfusion injury to varying degrees, but only 0.5 mg/kg pramipexole at 1, 3, 7 and 14 days consistently reduced modified neurological severity scores and improved neurological function in rats with global cerebral ischemia-reperfusion injury. In the open-field test, only 0.5 mg/kg pramipexole increased the number of entries into the central zone, duration spent in the central zone, total distance travelled in the open field and average velocity, which improved the spontaneous activities and reduced anxiety and depression of rats with global cerebral ischemia-reperfusion injury. 2. Different doses of pramipexole 0.25 mg/kg, 0.5 mg/kg, 1 mg/kg, and 2 mg/kg for 14 consecutive days significantly increased the number of surviving neurons in the hippocampal CA1 subfield in rats with global cerebral ischemia-reperfusion injury to varying degrees. Based on these results, we tentatively found that 0.5 mg/kg pramipexole may be the optimal dose in all of the above. 3. We found that 0.5 mg/kg pramipexole significantly increased the mitochondrial membrane potential in rats after global cerebral ischemia-reperfusion injury.

Conclusion

Different doses of dopamine receptor agonist pramipexole improved neurological function of rats with global cerebral ischemia-reperfusion injury to varying degrees, and 0.5 mg/kg pramipexole may be the optimal dose in all of the above. Pramipexole may produce neuroprotective effects by protecting neurons in the hippocampus and improving the mitochondrial membrane potential after global cerebral ischemia-reperfusion injury.

中文翻译：

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不同剂量多巴胺受体激动剂普拉克索对全脑缺血再灌注损伤大鼠神经行为及线粒体膜电位变化的影响

客观的

探讨不同剂量多巴胺受体激动剂普拉克索对全脑缺血再灌注损伤大鼠神经行为及线粒体膜电位变化的影响。

方法

75只SPF Sprague-Dawley雄性大鼠随机分为假手术组（n=20）、模型组（n=20）、普拉克索给药组（n=35）。采用改良的Pulsinelli四血管闭塞法制备全脑缺血再灌注损伤大鼠模型。普拉克索给药组对全脑缺血再灌注损伤大鼠腹腔注射普拉克索0.25 mg/kg、0.5 mg/kg、1 mg/kg、2 mg/kg不同剂量，每天1次，连续给药14天。根据改良神经严重程度评分、旷场试验和尼氏染色形态学的结果确定普拉克索的最佳剂量。采用JC-1荧光探针染色法测定普拉克索最佳给药剂量组线粒体膜电位。

结果

1. 不同剂量普拉克索0.25 mg/kg、0.5 mg/kg、1 mg/kg、2 mg/kg，连续14天对全脑缺血再灌注损伤大鼠给药，发现：四种剂量的普拉克索均可不同程度改善全脑缺血再灌注损伤大鼠的改良神经严重程度评分，但仅0.5 mg/kg普拉克索在第1、3、7、14天持续降低改良神经严重程度评分并改善神经功能全脑缺血再灌注损伤大鼠的功能。在开阔场地测试中，仅 0.5 mg/kg 普拉克索增加了进入中心区的次数、在中心区停留的时间、在开阔场地行进的总距离和平均速度，改善了全脑缺血再灌注损伤大鼠的自发活动，减轻了焦虑和抑郁。2.普拉克索0.25 mg/kg、0.5 mg/kg、1 mg/kg、2 mg/kg连续14 d显着增加全脑缺血再灌注大鼠海马CA1亚区存活神经元数量不同程度的受伤。基于这些结果，我们初步发现 0.5 mg/kg 普拉克索可能是上述所有情况下的最佳剂量。3.我们发现0.5 mg/kg普拉克索显着增加大鼠全脑缺血再灌注损伤后的线粒体膜电位。和2mg/kg连续14天，不同程度地显着增加全脑缺血再灌注损伤大鼠海马CA1亚区存活神经元的数量。基于这些结果，我们初步发现 0.5 mg/kg 普拉克索可能是上述所有情况下的最佳剂量。3.我们发现0.5 mg/kg普拉克索显着增加大鼠全脑缺血再灌注损伤后的线粒体膜电位。和2mg/kg连续14天，不同程度地显着增加全脑缺血再灌注损伤大鼠海马CA1亚区存活神经元的数量。基于这些结果，我们初步发现 0.5 mg/kg 普拉克索可能是上述所有情况下的最佳剂量。3.我们发现0.5 mg/kg普拉克索显着增加大鼠全脑缺血再灌注损伤后的线粒体膜电位。

结论

不同剂量的多巴胺受体激动剂普拉克索不同程度改善全脑缺血再灌注损伤大鼠的神经功能，0.5 mg/kg普拉克索可能是上述所有方法中的最佳剂量。普拉克索可能通过保护海马神经元和改善全脑缺血再灌注损伤后线粒体膜电位产生神经保护作用。