【摘要】 目的观察不同剂量右美托咪定对大鼠全脑缺血再灌注损伤的影响,探讨其神经保护作用及可能机制。方法将健康雄性SD大鼠40只随机分为假手术组(S组),全脑缺血再灌注对照组(C组),低、中、高剂量右美托咪定组(D1组、D2组、D3组),每组8只。采用四血管阻塞法制备全脑缺血再灌注模型。缺血即刻S组和C组静脉输注生理盐水2 m L/h;D1组、D2组、D3组分别静脉输注右美托咪定0.05,0.5,5μg/(kg·min),各组均持续输注2 h。于缺血再灌注后24 h用平衡木法和引体实验测定各组大鼠运动功能,干湿质量法测定各组大鼠脑组织含水量,ELISA法检测各组大鼠血清肿瘤坏死因子α(TNF-α)、白细胞介素-1β(IL-1β)的水平。结果与S组比较,C组和D1组、D2组、D3组大鼠运动功能均显著下降(P均<0.05),脑水含量显著增加(P均<0.05),血清TNF-α、IL-1β水平显著升高(P均<0.05)。与C组比较,D1组、D2组、D3组血清TNF-α、IL-1β水平均明显下降(P均<0.05);D1组对IL-1β的抑制作用强于D2组和D3组(P均<0.05),D2组和D3组比较差异无统计学意义;D1组、D2组、D3组对TNF-α的抑制作用差异无统计学意义。结论 0.05μg/(kg·min)右美托咪定对大鼠全脑缺血再灌注损伤有脑保护作用,可显著改善大鼠运动功能,其机制可能与抑制炎性因子有关。5μg/(kg·min)右美托咪定未显示出显著的脑保护效应。更多还原

【Abstract】 Objective It is to observe the effects of different doses of Dexmedetomidine on global cerebral ischemic-reperfusion injury in rats,and to investigate its neuroprotective effect and possible mechanism. Methods 40 male SD rats were randomly divided into 5 groups(n = 8 each) : sham operation group(group S),ischemic-reperfusion control group(group C),low,median and high doses of Dexmedetomidine groups(group D1-3). Global cerebral ischemic-reperfusion was induced by fourvessel occlusion. In group D1-3,immediately after ischemic,Dexmedetomidine 0. 05,0. 5 and 5 μg /(kg·min) were infused over 2 h respectively,while normal saline 2 m L / h were given instead of Dexmedetomidine in group S and C. The motor activity tests(beam-walking test and pull-up test) were carried out 24 h after reperfusion. The brain water content was detected by wet and dry weight method. Then blood samples were taken for measurement of plasma concentration of TNF-α and IL-1β by ELISA. Results Compared with group S,the motor activitives were significantly decreased(P < 0. 05),brain water content were significantly increased,levels of inflammatory factors TNF-α,IL-1β were all significantly rised in group C and D1-3(P < 0. 05). Compared with group C,the motor activity was significantly improved in group D1(P < 0. 05). The levels of inflammatory factors TNF-α,IL-1βwere significantly descented in group D1-3,especially in group D1(P < 0. 05). Conclusion The low dose of Dexmedetomidine 0. 05 μg /(kg·min) shows an neuroprotective effect against ischemic-reperfusion brain injury,the mechanism of protection may be related to inhibiting the injury of free radicals and maintaining the integrity of glial cells.更多还原