Etomidate protects retinal ganglion cells from hydrogen peroxide-induced injury via Nrf2/HO-1 pathway  

作　　者：Xuan Zhao De-Gang Fan Xin-Chao Zhang Si-Wei You Fang Kuang Ming-Mei Wu 

机构地区：[1]Department of Histology and Embryology,School of Basic Medical Sciences,Xi’an Medical University,Xi’an 710021,Shaanxi Province,China [2]Department of Neurobiology,the Basic Medical Science Academy,the Fourth Military Medical University,Xi’an 710032,Shaanxi Province,China [3]Department of Spinal Surgery,Honghui Hospital,Xi’an Jiaotong University,Xi’an 710054,Shaanxi Province,China [4]College of Life Sciences,Northwestern University,Xi’an 710069,Shaanxi Province,China

出　　处：《International Journal of Ophthalmology(English edition)》2024年第9期1606-1613,共8页国际眼科杂志（英文版）

基　　金：Supported by the Ministry of Science and Technology of China(No.2021ZD0203104);the Science and Technology Plan Project of Shaanxi Province of China(No.2022SF-497);Xi’an Medical University Doctoral Research Fund(No.2020DOC18).

摘　　要：AIM:To determine whether etomidate(ET)has a protective effect on retinal ganglion cells(RGCs)injured with hydrogen peroxide(H_(2)O_(2))and to explore the potential mechanism underlying the antioxidative stress effect of ET.METHODS:Cultured RGCs were identified by double immunofluorescent labeling of microtubule-associated protein 2 and Thy1.1.An injury model of H_(2)O_(2)-induced RGCs oxidative stress was established in vitro.Cells were pretreated with different concentrations of ET(1,5,and 10μmol/L)for 4h,followed by further exposure to H_(2)O_(2)at 1000μmol/L.Cell counting kit 8 and Annexin V/propidium iodide assays were applied to detect the viabilities and apoptosis rates of the RGCs at 12,24,and 48h after H_(2)O_(2)stimulation.The levels of nitric oxide,malondialdehyde,and glutathione in culture media were measured at these time points.Quantitative reverse transcription polymerase chain reaction(qRT-PCR)and Western blot were performed to observe the effects of ET on the messenger RNA and protein expression of inducible nitric oxide synthase(iNOS),nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase 1(HO-1),glutathione peroxidase 1 and the level of conjugated acrolein in RGCs at 12,24,and 48h after H_(2)O_(2)stimulation and in the retina at 12h after optic nerve transection(ONT).RESULTS:The applications of 5 and 10μmol/L of ET significantly increased the viability of RGCs.Results from qRT-PCR indicated a decrease in the expression of iNOS and an increase in the expressions of Nrf2 and HO-1 in ETpretreated RGCs at 12,24 and 48h after H_(2)O_(2)stimulation,as well as in ET-treated retinas at 12h after ONT.Western blot analysis revealed a decrease in the expression of iNOS and levels of conjugated acrolein,along with an increase in the expressions of Nrf2 and HO-1 in ET-pretreated RGCs in vitro and ET-treated retinas in vivo.CONCLUSION:ET is a neuroprotective agent in primary cultured RGCs injured by H_(2)O_(2).The effect of ET is dosedependent with the greatest effect being at 10μmol/L.ET plays

关 键 词：ETOMIDATE retinal ganglion cell NEUROPROTECTION hydrogen peroxide-induced injury nuclear factor erythroid 2-related factor 2 heme oxygenase 1 

分 类 号：R774.1[医药卫生—眼科]