摘要
目的:探讨右美托咪定通过调控核因子E2相关因子2(Nrf2)/血红素氧合酶-1(HO-1)通路对过氧化氢(H2O2)诱导的心肌细胞氧化应激损伤发挥保护作用。方法:体外培养H9c2心肌细胞,选择对数生长期细胞进行实验,分为对照组、模型组、右美托咪定低、中、高剂量组。对照组不进行处理;模型组加入终浓度为200μmol·L^-1的H2O2;右美托咪定低、中、高剂量组分别加入终浓度为5,10,20μmol·L^-1的右美托咪定,同时给予终浓度为200μmol·L^-1的H2O2,继续培养24 h后,检测各组细胞存活率、凋亡率、细胞中抗氧化指标、一氧化氮(NO)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、HO-1和Nrf2蛋白变化情况。结果:与对照组相比,模型组和右美托咪定各剂量组H9c2细胞存活率、谷胱甘肽(GSH)、NO、HO-1和Nrf2蛋白水平降低(P<0.05),凋亡率、乳酸脱氢酶(LDH)、丙二醛(MDA)、活性氧(ROS)、TNF-α和IL-6升高(P<0.05);与模型组相比,右美托咪定各剂量组H9c2细胞存活率、GSH、NO、HO-1和Nrf2蛋白水平升高(P<0.05),凋亡率、LDH、MDA、ROS、TNF-α和IL-6降低(P<0.05),且右美托咪定各剂量组之间上述指标呈剂量依赖性(P<0.05)。结论:右美托咪定可能通过激活Nrf2/HO-1通路,减轻心肌细胞的氧化损伤,促进细胞增殖和抑制细胞凋亡,从而发挥心肌保护作用。
Objective:To investigate the protective effect of dexmedetomidine on oxidative stress injury induced by hydrogen peroxide(H2O2)in cardiomyocytes by regulating nuclear factor erythroid-2 related factor2(Nrf2)/heme oxygenase-1(HO-1)pathway.Methods:H9c2 cardiomyocytes were cultured in vitro,and logarithmic growth phase cells were selected for the experiment.The cells were divided into the control group,the model group,and low,medium and high dose dexmedetomidine groups.The cells in the control group were without any treatment,and the cells in the model group were treated with hydroxyapatite at the final concentration of 200μmol·L^-1 H2O2;the cells in the low,middle and high dose dexmedetomidine groups were treated with dexmedetomidine respectively at the final concentration of 5,10 and 20μmol·L^-1,and hydroxyapatite at the final concentration of 200μmol·L^-1.After the continuous culture for 24 hours,the changes of cell survival rate,apoptosis rate,antioxidant index,nitric oxide(NO),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),HO-1 and Nrf2 protein were detected.Results:Compared with those in the control group,the survival rate,glutathione(GSH),NO,HO-1 and Nrf2 protein levels of H9c2 cells in the model group and all dexmedetomidine groups were decreased(P<0.05),while the apoptotic rate,lactate dehydrogenase(LDH),malondialdehyde(MDA),reactive oxygen species(ROS),TNF-αand IL-6 were increased(P<0.05).Compared with those in the model group,the survival rate,GSH,NO,HO-1 and Nrf2 protein levels of H9c2 cells in all dexmedetomidine groups were increased(P<0.05),and the apoptotic rate,LDH,MDA,ROS,TNF-αand IL-6 were decreased(P<0.05),and the above indices were dose-dependent among dexmedetomidine groups(P<0.05).Conclusion:Dexmedetomidine may play a protective role in myocardium by activating Nrf2/HO-1 pathway,alleviating oxidative damage,promoting cell proliferation and inhibiting cell apoptosis.
作者
杜佳楠
戴勤学
徐夏
容凤娇
Du Jianan;Dai Qinxue;Xu Xia;Rong Fengjiao(Department of Anesthesiology,Sanya Central Hospital,Hainan Sanya 572000,China;Department of Anesthesiology,the First Affiliated Hospital of Wenzhou Medical University)
出处
《中国药师》
CAS
2020年第9期1691-1695,共5页
China Pharmacist
