SIRT3介导CypD去乙酰化在右美托咪定减轻肾缺血再灌注损伤中的作用  

Role of SIRT3-mediated CypD deacetylation in dexmedetomidine-induced reduction of renal ischemia-reperfusion injury in rats

作　　者：斯妍娜[1] 张媛[1] 韩流[1] 陈利海[1] 徐亚杰[1] 孙凡[1] 潘笑笑 鲍红光[1] 

机构地区：[1]南京医科大学附属南京医院(南京市第一医院)麻醉科,210006

出　　处：《中华麻醉学杂志》2016年第2期239-241,共3页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（81401620）;南京市医学科技发展项目（YKK12085）

摘　　要：目的评价沉默信息调节因子2相关酶3（SIRT3）介导亲环素D（CypD）去乙酰化在右美托咪定减轻大鼠肾缺血再灌注损伤中的作用。方法健康雄性SD大鼠32只，3～4月龄，体重210～290g，采用随机数字表法分为4组（n=8）：假手术组（Sham组）、缺血再灌注组（I／R组）、右美托咪定组（Dex组）和SIRT3抑制剂Tenovin-6组（Tenovin-6组）。采用肾缺血45min，再灌注48h的方法制备肾缺血再灌注损伤模型。Dex组和Tenovin-6组于缺血前30min时腹腔注射右美托咪定50p,g／kg；Tenovin-6组于给予右美托咪定前1h时腹腔注射Tenovin-650mg／kg。再灌注48h时，取肾组织，光镜下观察病理学结果，采用TUNEL法检测细胞凋亡情况，计算细胞凋亡指数，采用Western blot法检测CypD的乙酰化水平；提取线粒体，测定线粒体通透性转换孔（mPTP）的开放程度。结果与Sham组比较，I／R组、Dex组和Tenovin-6组肾组织细胞凋亡指数、CypD乙酰化水平和mPTP开放程度均升高（P〈0．05），病理学损伤加重；与I／R组比较，Dex组肾组织细胞凋亡指数、CypD乙酰化水平和mPTP开放程度均降低（P〈0．05），病理学损伤减轻；与Dex组比较，Tenovin-6组肾组织细胞凋亡指数、CypD乙酰化水平和mPTP开放程度均升高（P〈0．05），病理学损伤加重。结论SIRT3介导的CypD去乙酰化参与了右美托咪定减轻大鼠肾缺血再灌注损伤的过程。Objective To evaluate the role of silent information regulator 2 homolog 3 （SIRT3）- mediated cyclophilin D （CypD） deacetylation in dexmedetomidine-induced reduction of renal ischemiareperfusion （I/R） injury in rats. Methods Thirty-two male Sprague-Dawley rats, aged 3-4 months, weighing 210-290 g, were randomly allocated into 4 groups （n = 8 each） using a random number table： sham operation group （Sham group） , I/R group, dexmedetomidine group （Dex group） , and SIRT3 inhibitor Tenovin-6 group （Tenovin-6 group）. Renal I/R was induced by occlusion of renal pedicles for 45 rain followed by 48 h of reperfusion in rats anesthetized with phenobarbital sodium. Dexmedetomidine 50 μg/kg was injected intraperitoneally at 30 min prior to ischemia in Dex and Tenovin-6 groups. Tenovin-6 50 mg/kg was injected intraperitoneally at 1 h prior to dexmedetomidine administration in group Tenovin-6. At 48 h of reperfusion, renal tissues were obtained for examination of pathological changes （under light microscope）, and for determination of cell apoptosis （by TUNEL）, and CypD acetylation （by Western blot）. The apoptosis index was calculated. The mitochondria were extracted for determination of mitochondrial permeability transition pore （mPTP） opening. Results Compared with group Sham, the apoptosis index, CypD acetylation and mPTP opening were significantly increased （P〈0.05） , and the pathological changes were aggravated in I/R, Dex and Tenovin-6 groups. Compared with group I/R, the apoptosis index, CypD acetylation and mPTP opening were significantly decreased （P〈0.05） , and the pathological changes were attenuated in group Dex. Compared with group Dex, the apoptosis index, CypD acetylation and mPTP opening were significantly increased （P〈0.05） , and the pathological changes were aggravated in group Tenovin-6. Conclusion SIRT3-mediated CypD deacetylation is involved in dexmedetomidine-induced reduction of renal I/R injury in rats.

关 键 词：右美托咪啶 再灌注损伤 肾 抗衰老酶 亲环素类 

分 类 号：R614[医药卫生—麻醉学]