淺低溫聯(lián)合線粒體分裂抑制劑減輕全腦缺血-再灌注后線粒體損傷
發(fā)布時(shí)間:2018-06-27 09:29
本文選題:淺低溫 + 線粒體分裂抑制劑; 參考:《臨床麻醉學(xué)雜志》2017年07期
【摘要】:目的觀察淺低溫聯(lián)合線粒體分裂抑制劑(mitochondrial division inhibitor 1,Mdivi-1)對(duì)大鼠海馬缺血-再灌注(ischemia-reperfusion,IR)損傷后線粒體的影響。方法健康清潔級(jí)雄性SD大鼠40只,體重280~320g,采用隨機(jī)數(shù)字表法分為五組:假手術(shù)組(Sham組)、全腦IR組(IR組)、淺低溫組(H組)、線粒體分裂抑制劑組(M組)和淺低溫聯(lián)合線粒體分裂抑制劑組(HM組),每組8只。采用經(jīng)食管心臟起搏誘發(fā)心跳驟停+心肺復(fù)蘇方法制備大鼠全腦IR損傷模型,即缺血4min,再灌注6h。Sham組不經(jīng)歷心跳驟停和心肺復(fù)蘇,其余操作與IR組一致;H組和HM組于再灌注即刻體表降溫,15min之內(nèi)將直腸溫度降至32~34℃,自制變溫箱維持6h,其余組維持正常體溫;M組和HM組于再灌注即刻靜脈注射Mdivi-1(1.2 mg/kg),其余組注射等容積二甲基亞砜(DMSO)。于再灌注6h處死大鼠取雙側(cè)海馬,采用Western blot法檢測(cè)線粒體發(fā)動(dòng)相關(guān)蛋白-1(dynamin-related protein 1,Drp1)和細(xì)胞色素C(cytochrome Cyt-C)蛋白含量,電鏡下觀察海馬區(qū)椎體細(xì)胞中線粒體結(jié)構(gòu)形態(tài)。結(jié)果 IR組、H組、M組和HM組Drp1和Cyt-C蛋白含量明顯高于Sham組(P0.05);H組、M組和HM組Drp1和Cyt-C蛋白含量明顯低于IR組(P0.05);HM組Drp1和Cyt-C蛋白含量明顯低于H組和M組(P0.05),H組和M組Cyt-C蛋白含量差異無(wú)統(tǒng)計(jì)學(xué)意義。Sham組線粒體呈短棒狀,結(jié)構(gòu)清晰完整,其他各組中可見(jiàn)不同程度的線粒體分裂,膜間隙腫脹,基質(zhì)包含物沉積,空泡形成,嵴模糊或消失,HM組病變較輕。結(jié)論淺低溫聯(lián)合線粒體分裂抑制劑可以減輕大鼠全腦缺血-再灌注后線粒體損傷,聯(lián)合效果優(yōu)于單獨(dú)應(yīng)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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