Nrf2/ARE通路介导右美托咪定减轻肢体缺血/再灌注损伤中的作用

doi:10.13459/j.cnki.cjap.2016.03.016

中国应用生理学杂志 ›› 2016, Vol. 32 ›› Issue (3): 250-254.doi: 10.13459/j.cnki.cjap.2016.03.016

Nrf2/ARE通路介导右美托咪定减轻肢体缺血/再灌注损伤中的作用

袁培根, 薛彬彬, 林碧, 赵喜越, 周森, 胡一, 包财盈, 林丽娜

温州医科大学附属第一医院, 浙江温州 325000

收稿日期:2015-07-13 修回日期:2015-11-10 出版日期:2016-05-28 发布日期:2018-06-12
通讯作者: 林丽娜,Tel:0577-88069790;E-mail:wzlinlina@163.com E-mail:wzlinlina@163.com
基金资助:
温州市科技计划项目（Y20140561）

Nrf2/ARE pathway mediates the reducing effect of Dexmedeto-midine on ischemia/reperfusion injury in skeletal muscle

YUAN Pei-gen, XUE Bin-bin, LIN Bi, ZHAO Xi-yue, ZHOU Sen, HU Yi, BAO Cai-ying, LIN Li-na

The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China

Received:2015-07-13 Revised:2015-11-10 Online:2016-05-28 Published:2018-06-12
Supported by:
温州市科技计划项目（Y20140561）

摘要/Abstract

摘要： 目的：观察Nrf2/ARE通路在右美托咪定（DEX）预处理减轻大鼠肢体缺血/再灌注损伤中的作用。方法：28只成年雄性SD大鼠随机分为4组（n=7）：假手术组（Sham组）、缺血再灌注组（I/R组）、I/R+右美托咪定预处理组（DEX组）、I/R+DEX+阿替美唑组（Atip组）。Atip组在麻醉后腹腔一次性给予Atip （250 μg/kg）和DEX （25 μg/kg），Sham组和I/R组在麻醉后腹腔给予相应体积生理盐水，DEX组给予相应体积DEX和生理盐水，30 min后单侧股部切口，无创动脉夹夹闭股动脉，侧支循环用橡皮筋以恒定张力结扎，缺血3 h后去除动脉夹及橡皮筋，开放2 h后，取大鼠血清测乳酸脱氢酶（LDH）、肌酸激酶（CK）；取部分腓肠肌，测量丙二醛（MDA）、超氧化物歧化酶（SOD）以及Western blot检测胞核核因子E2相关因子2（Nrf2）、胞浆HO-1蛋白；免疫组化检测胞核Nrf2、胞浆HO-1蛋白和光镜观察骨骼肌形态；同时切取少量腓肠肌进行湿干比检测。结果：与Sham组相比，I/R组湿干比、MDA、LDH、CK、Nrf2、HO-1蛋白表达明显升高（P<0.05），SOD活性显著降低（P<0.05）；与I/R组相比，DEX组湿干比、MDA、LDH、CK明显降低（P<0.05），SOD、Nrf2、HO-1蛋白表达显著增多（P<0.05）；与DEX组相比，Atip恰能扭转DEX的这种作用，Atip组各指标与DEX组有显著差异（P<0.05）。结论：Nrf2蛋白存在于大鼠的骨骼肌中并且DEX可以通过α2受体上调核内Nrf2水平，使Nrf2下游的HO-1保护蛋白增多，起到抗氧化的作用。

关键词: 缺血/再灌注损伤, 氧化应激, 核因子E2相关因子2, 右美托咪定, 大鼠

Abstract: Objective:To explore the role of Nrf2/ARE pathway in skeletal muscle ischemia/reperfusion(I/R) injury preconditioning by dexmedetomidine(DEX). Methods:Twenty-eight SD rats were randomly divided into sham-operated(Sham group)、I/R group、I/R+ DEX(DEX group) and I/R+DEX +Atipamezole (Atip group). In the Atip group, Atip(250 μg/kg) and DEX(25 μg/kg) were injected together after anesthesia; In the Sham and I/R groups, the homologous saline was also injected at the same time; In the DEX group, the homologous DEX and saline were coinjected. After 30 minutes, the hind limb ischemia was induced by clamping the common femoral artery and ligaturing collateral circulation. After 3 h of ischemia, the clamp and tourniquet were removed and the rats underwent 2 h of reperfusion. We measured plasma concentrations of lactate dehydrogenase (LDH) and creatine kinase(CK). The gastrocnemius muscle was harvested and immediately stored at -80℃ for the assessment of malondialdehyde(MDA)、superoxide dismutase(SOD) and Nrf2/HO-1 protein detected by Western blot. The other section muscle was stored in triformol for immunohistochemical and HE staining. The wet/dry was also immediately detecting. Results:The levels of wet/dry、MDA、LDH、CK、Nrf2 and HO-1 were higher(P<0.05) while the level of SOD was lower(P<0.05) in the I/R group than those in sham group. The levels of wet/dry、MDA、LDH、CK were significantly lower(P<0.05) yet the levels of SOD and Nrf2/HO-1 were significantly higher(P<0.05) in DEX group than those in I/R group. However, Atip reversed the effect of DEX in Atip group, each of indicators had significant changes compared with those in the DEX group(P<0.05). Conclusion:Nrf2 protein was expressed in skeletal muscle of rat and DEX could promote its level in nucleus by α-adrenergic receptor. The down-stream products of Nrf2 have the effect of antioxidant.

Key words: ischemia/reperfusion injury, oxidative stress, NF-E2-related factor-2, dexmedetomidine, rat

袁培根, 薛彬彬, 林碧, 赵喜越, 周森, 胡一, 包财盈, 林丽娜. Nrf2/ARE通路介导右美托咪定减轻肢体缺血/再灌注损伤中的作用[J]. 中国应用生理学杂志, 2016, 32(3): 250-254.

YUAN Pei-gen, XUE Bin-bin, LIN Bi, ZHAO Xi-yue, ZHOU Sen, HU Yi, BAO Cai-ying, LIN Li-na. Nrf2/ARE pathway mediates the reducing effect of Dexmedeto-midine on ischemia/reperfusion injury in skeletal muscle[J]. CJAP, 2016, 32(3): 250-254.

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Nrf2/ARE通路介导右美托咪定减轻肢体缺血/再灌注损伤中的作用

Nrf2/ARE pathway mediates the reducing effect of Dexmedeto-midine on ischemia/reperfusion injury in skeletal muscle

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