右美托咪啶预处理对大鼠缺氧缺血性脑损伤的影响

Effects of dexmedetomidine preconditioning on cerebral hypoxia-ischemia injury in rats

目的探讨右美托咪啶预处理对缺氧缺血性脑损伤的保护作用。方法采用窒息后心跳骤停法建立大鼠缺氧缺血性脑损伤模型,并于窒息前静脉注射负荷剂量的右美托咪啶4μg/kg;分别于大鼠窒息前后行血气分析,心肺复苏后行神经功能缺损程度评价,以及海马组织形态学和超微结构观察。结果窒息后常规复苏组和右美托咪啶组大鼠动脉血氧分压下降(P=0.000)、二氧化碳分压升高(P=0.000);常规复苏组大鼠不同观察时间点神经功能缺损量表(NDS)评分均高于假手术组(P=0.000),右美托咪啶组心肺复苏后24、48和72 h时NDS评分低于常规复苏组(均P=0.000)。与常规复苏组相比,右美托咪啶组大鼠海马神经元坏死、核固缩、核溶解程度明显减轻,存活的神经元数目明显增多,水肿改善;神经元无明显脱髓鞘改变,神经血管单元微环境良好。结论右美托咪啶预处理可有效减轻缺氧缺血性脑损伤后神经功能缺损程度,改善海马组织超微结构变化。

Objective To investigate the effects of dexmedetomidine preconditioning on cerebral bypoxia-isehemia injury in rats. Methods Seventy-two adult male Sprague-Dawley （SD） rats weighing 250-300 g were randomly divided into 3 groups： sham group （Group S）, conventional resuscitation group （Group C） and dexmedetomidine preconditioning group （Group D）. Cerebral hypoxia-isehemia injury rat model was produced by mechanical asphyxia. In Group D, 4μ g/kg dexmedetomidine was injected intravenously 5 rain before asphyxia. The Neurological Deficit Scale （NDS） was assessed at 12, 24, 48 and 72 h after return of spontaneous circulation. Six rats were sacrificed in each group and brain tissues were removed for microscopic examination of hippoeampal CA1 region and ultrastructure by electron microscope. Results The PaO2 in Group D and C rats was significantly lower after resuscitation （P = 0.000, for all）, while the PaCO2 was increased as compared with before asphyxia （P = 0.000, for all）. Compared with Group S, NDS at each time point were significantly increased in Group C （P = 0.000, for all）. Compared with Group C, NDS were significantly decreased at 24, 48 and 72 h in Group D （P = 0.000, for all）. Compared with Group C, hippocampal neurons in Group D revealed alleviative necrosis, karyopyknosis and karyolysis, as well as increased number of survival neurons and relieved edema. Besides, there was good microenvironment of neurovaseular unit and no obvious demyelination. Conclusions Dexmedetomidine preconditioning can attenuate cerebral hypoxia-ischemia injury in rats, and improve the pathologic changes and ultrastructure of neurons of hippocampus.