地氟烷介导Nrf2通路并抑制NF-κB活化缓解脑缺血再灌注大鼠氧化损伤和炎症反应的研究  

Study of desflurane relieving oxidative damage and inflammation response in rats undergoing cerebral ischemia-reperfusion by mediating Nrf2 pathway and inhibiting NF-κB activation

作　　者：赵红雷 赵翠党 朱会利 任光辉[3] 李兴 姜天宝 ZHAO Hong-lei;ZHAO Cui-dang;ZHU Hui-li(Department of Anesthesiology,Handan First Hospital,Handan Hebei 056001,China;Department of Anesthesiology,Handan Ophthalmic Hospital,Handan Hebei 056001,China;Department of Surgery,Handan First Hospital,Handan Hebei 056001,China)

机构地区：[1]邯郸市第一医院麻醉科,河北邯郸056001 [2]邯郸市眼科医院麻醉科,河北邯郸056001 [3]邯郸市第一医院外科,河北邯郸056001 [4]邯郸市第一医院手术室,河北邯郸056001

出　　处：《临床和实验医学杂志》2022年第10期1009-1013,共5页Journal of Clinical and Experimental Medicine

基　　金：河北省科学技术厅课题(编号:182777138)。

摘　　要：目的探究地氟烷在脑缺血再灌注(IR)大鼠中经由介导核因子E2相关因子2(Nrf2)通路并抑制核因子-κB(NF-κB)活化缓解氧化损伤和炎症反应机制。方法选择60只成年雄性大鼠随机数字表法分为3组,每组各20只,依次为假手术组、IR组以及地氟烷组。假手术组仅进行静脉与动脉穿刺,IR组采用全身低血压与双侧颈总动脉夹闭方式构建IR模型,缺血10 min后恢复灌注,地氟烷组在IR模型构建前应用5.9%浓度(1.0 MAC)地氟烷吸入处理1 h,空气洗脱后进行1 d再灌注后测定并比较大鼠脑梗死面积以及脑神经损伤评分,脑组织Nrf2信号通路指标mRNA与相关蛋白,血清氧化应激指标[谷胱甘肽(GSH)、超氧化物歧化酶(SOD)、丙二醛],NF-κB活化指标mRNA与相关蛋白,血清炎症因子指标[白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)]水平。结果与假手术组比较,IR组大鼠脑神经损伤以及脑梗死体积均显著增加,地氟烷组大鼠脑神经损伤以及脑梗死体积均显著低于IR组,差异均有统计学意义(P<0.05)。IR组大鼠脑组织Nrf2、抗氧化反应元件(ARE)mRNA和Nrf2、血红素加氧酶-1(HO-1)、醌氧化还原酶1(NQO1)蛋白均显著低于假手术组,而地氟烷组大鼠Nrf2、ARE mRNA和Nrf2、HO-1和NQO1蛋白均显著高于IR组,差异均有统计学意义(P<0.05)。IR组大鼠血清GSH、SOD水平均显著低于假手术组,丙二醛显著高于假手术组,而地氟烷组大鼠血清GSH、SOD水平均显著高于IR组,丙二醛显著低于IR组,差异均有统计学意义(P<0.05)。IR组大鼠脑组织NF-κB mRNA和蛋白、Toll样受体4(TLR4)mRNA水平均显著高于假手术组,半胱氨酸蛋白酶3(caspase-3)、Bcl-2、Bax蛋白水平均显著低于假手术组,而地氟烷组大鼠脑组织NF-κB、TLR4 mRNA均显著低于IR组,NF-κB、Caspase-3、Bax蛋白均显著低于IR组,Bcl-2蛋白显著高于IR组,差异均有统计学意义(P<0.05)。IR组大鼠血清IL-6、TNF-α水平均显著高于假手术组,地�Objective To explore the mechanism of desflurane on relieving oxidative damage and inflammation response in rats undergoing cerebral ischemia-reperfusion(IR)by mediating nuclear factor erythroid-2 related factor 2(Nrf2)pathway and inhibiting nuclear factor-κB(NF-κB)activation.Methods Sixty adult male rats were enrolled and randomly divided into sham operation group,IR group and desflurane group,20 cases in each group.In the sham operation group,only venous and arterial puncture was performed.IR model was constructed by systemic hypotension and bilateral common carotid artery occlusion.The perfusion was continued at 10 minutes after ischemia.Before the construction of IR model,desflurane group was treated with 5.9%(1.0 MAC)desflurane inhalation for 1h,and given 1 h reperfusion after air dehydration.The cerebral infarction area,score of brain nerve injury,mRNA and related proteins of Nrf2 signaling pathway indexes in brain tissue,serum oxidative stress indexes[glutathione(GSH)and superoxide dismutase(SOD),malondialdehyde(MAD)],mRNA and related proteins of NF-κB activation indexes,and levels of serum inflammation factors indexes[interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)]of rats were measured and compared.Results The score of brain nerve injury and cerebral infarction volume in the IR group were significantly higher than those in the sham operation group,the score of brain nerve injury and cerebral infarction volume in the desflurane group were significantly lower than those in the IR group,and the differences were statistically significant(P<0.05).Nrf2 and antioxidant reaction element(ARE)mRNA and Nrf2,heme oxygenase-1(HO-1),quinone oxidoreductase 1(NQO1)proteins in the IR group were significantly lower than those in the sham operation group,Nrf2 and ARE mRNA,Nrf2,HO-1,NQO1 proteins in the desflurane group were significantly higher than those in the IR group,and the differences were statistically significant(P<0.05).The levels of serum GSH and SOD in IR group were significantly lower than those in sham

关 键 词：大鼠 地氟烷 Nrf2通路 NF-ΚB活化 脑缺血再灌注 氧化损伤 炎症反应 

分 类 号：R614[医药卫生—麻醉学]