右美托咪定预处理对大鼠脑缺血再灌注损伤及自噬的影响

Effects of dexmedetomidine pretreatment on cerebral ischemia-reperfusion injury and autophagy in rats

目的研究右美托咪定(Dex)对大鼠脑缺血再灌注(I/R)损伤及自噬的影响。方法 36只SD大鼠随机分为对照组、I/R组和Dex组,每组12只。采用线栓法建立脑I/R模型,对照组不做任何预处理;I/R组在造模前30 min,腹腔注射0.25ml生理盐水;Dex预处理组在造模前30 min给予右美托咪定50μg/kg,用生理盐水稀释至0.25 ml腹腔注射。再灌注24 h,进行神经功能评分,2,3,5-氯化三苯基四氮唑(TTC)染色检测脑梗死面积,透射电镜观察自噬小体的形成,Western blot检测自噬标志基因Beclin-1、LC3及自噬信号通路分子p-AMPK的表达。结果 I/R组的神经功能评分、脑梗死体积及缺血脑组织中Beclin-1、LC3-Ⅱ/LC3-Ⅰ、p-AMPK的表达水平均高于对照组,差异有统计学意义(P<0.05)。Dex组神经功能评分、脑梗死面积均低于I/R组,缺血脑组织中Beclin-1、LC3-Ⅱ/LC3-Ⅰ、p-AMPK的表达水平均高于I/R组,差异均有统计学意义(P<0.05)。结论 Dex可能通过激活AMPK通路减轻大鼠脑I/R损伤并促进自噬。

Objective To study the effect of dexmedetomidine(Dex)pretreatment on cerebral ischemia-reperfusion(I/R)injury and autophagy in rats.Methods Thirty-six SD rats were randomly divided into three groups:control group,I/R group and Dex pretreatment group,with 12 rats in each group.Brain I/R model was established by suture-occluded method.The rats in I/R group were intraperitoneally injected with 0.25 ml saline at 30 min before modeling.The rats in Dex pretreatment group were intraperitoneally given 50μg/kg Dex(diluted to 0.25 ml by normal saline)at 30 min before modeling.At 24 h after reperfusion,the neurological function was scored,the cerebral infarction area was detected by 2,3,5-triphenyltetrazolium chloride(TTC)staining,the formation of autophagosome was observed under transmission electron microscopy,and the expression levels of autophagy marker gene Beclin-1,LC3 and autophagy signaling pathway molecule p-AMPK were detected by Western blot.Results The neurological score,the infarct volume and the expression levels of Beclin-1,LC3-Ⅱ/LC3-Ⅰand p-AMPK in ischemic brain tissues were significantly higher in I/R group than in control group(P<0.05).The neurological score and the infarct area in Dex pretreatment group were lower than those in I/R group,while the expression levels of Beclin-1,LC3-Ⅱ/LC3-Ⅰand p-AMPK in ischemic brain tissues were statistically higher than those in I/R group(P<0.05).Conclusion Dex medetomidine can reduce the brain I/R injury and promote autophagy in rats by activating AMPK pathway.