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浅低温联合线粒体分裂抑制剂减轻全脑缺血-再灌注后线粒体损伤

发布时间:2018-06-27 09:29

  本文选题:浅低温 + 线粒体分裂抑制剂 ; 参考:《临床麻醉学杂志》2017年07期


【摘要】:目的观察浅低温联合线粒体分裂抑制剂(mitochondrial division inhibitor 1,Mdivi-1)对大鼠海马缺血-再灌注(ischemia-reperfusion,IR)损伤后线粒体的影响。方法健康清洁级雄性SD大鼠40只,体重280~320g,采用随机数字表法分为五组:假手术组(Sham组)、全脑IR组(IR组)、浅低温组(H组)、线粒体分裂抑制剂组(M组)和浅低温联合线粒体分裂抑制剂组(HM组),每组8只。采用经食管心脏起搏诱发心跳骤停+心肺复苏方法制备大鼠全脑IR损伤模型,即缺血4min,再灌注6h。Sham组不经历心跳骤停和心肺复苏,其余操作与IR组一致;H组和HM组于再灌注即刻体表降温,15min之内将直肠温度降至32~34℃,自制变温箱维持6h,其余组维持正常体温;M组和HM组于再灌注即刻静脉注射Mdivi-1(1.2 mg/kg),其余组注射等容积二甲基亚砜(DMSO)。于再灌注6h处死大鼠取双侧海马,采用Western blot法检测线粒体发动相关蛋白-1(dynamin-related protein 1,Drp1)和细胞色素C(cytochrome Cyt-C)蛋白含量,电镜下观察海马区椎体细胞中线粒体结构形态。结果 IR组、H组、M组和HM组Drp1和Cyt-C蛋白含量明显高于Sham组(P0.05);H组、M组和HM组Drp1和Cyt-C蛋白含量明显低于IR组(P0.05);HM组Drp1和Cyt-C蛋白含量明显低于H组和M组(P0.05),H组和M组Cyt-C蛋白含量差异无统计学意义。Sham组线粒体呈短棒状,结构清晰完整,其他各组中可见不同程度的线粒体分裂,膜间隙肿胀,基质包含物沉积,空泡形成,嵴模糊或消失,HM组病变较轻。结论浅低温联合线粒体分裂抑制剂可以减轻大鼠全脑缺血-再灌注后线粒体损伤,联合效果优于单独应用。
[Abstract]:Objective to observe the effects of mild hypothermia combined with mitochondrial mitotic inhibitor (mitochondrial division inhibitor 1 / Mdivi-1 on mitochondria after ischemia-reperfusion (IR) injury in hippocampus of rats. Methods 40 healthy and clean male SD rats were used. Body weight 280 ~ 320g was randomly divided into five groups: sham-operated group (Sham group), whole brain IR group (IR group), mild hypothermia group (H group), mitochondrial mitotic inhibitor group (M group) and mild hypothermia combined with mitochondrial mitotic inhibitor group (HM group) with 8 rats in each group. The whole brain IR injury model was established by cardiac arrest induced cardiopulmonary resuscitation by transesophageal cardiac pacing in rats, I. E. ischemia for 4 min, reperfusion for 6 h. Sham group did not experience cardiac arrest and cardiopulmonary resuscitation. The rest of the operation was consistent with that of IR group. The rectal temperature in H group and HM group was reduced to 32 鈩,

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