临床眼科杂志2026，Vol.34Issue(2)：97-103,7.DOI:10.3969/j.issn.1006-8422.2026.02.001
胃饥饿素对高糖诱导的视网膜血管内皮细胞铜死亡的影响
Effect of ghrelin on cuproptosis induced by high glucose in retinal vascular endothelial cells
摘要
Abstract
Objective To observe the effect of ghrelin on cuproptosis of human retinal microvascular endothelial cells(HRMECs)induced by high glucose.Methods A prospective case-control study.HRMECs cultured in vitro were randomly divided into the control group(5.5 mmol·L⁻¹ glucose)and the high glucose group(30 mmol·L⁻¹ glucose),and were cultured for 24,48,and 96 hours.The copper ion concentration in both groups was measured using a copper ion de-tection kit to determine the effect duration of high glucose.Western blot was performed to assess the expression of key cop-per death molecules Lipoy-DLAT,Lipoy-DLST and FDX1.The cell viability of each group was measured by CCK-8 assay.Subsequently,HRMECs were randomly assigned to the control group,high glucose group,and high glucose+ghrelin group(30 mmol·L⁻¹ glucose and 10 nmol·L⁻¹ ghrelin)and cultured for 48 hours.The copper ion concentration,protein ex-pression of Lipoy-DLAT and Lipoy-DLST,and cell viability were measured using the same assays.Additionally,quantita-tive polymerase chain reaction(PCR)was employed to detect the mRNA expression of FDX1,and MeRIP-qPCR was used to assess the m6A modification of FDX1-mRNA.Results Copper ion concentration measurements revealed a significant increase in copper ion levels in HRMECs after 24 hours of high glucose stimulation,which continued to rise with prolonged exposure.Compared to the control group,the high glucose group exhibited increased expression of Lipoy-DLAT,Lipoy-DLST,and FDX1 proteins(all P<0.05),while cell viability significantly decreased(P<0.05).Following ghrelin treat-ment,the copper ion concentration,as well as the protein expression of Lipoy-DLAT and Lipoy-DLST in the high glucose+ghrelin group,were lower than those in the high glucose group,and cell viability significantly recovered compared to the high glucose group(all P<0.05).Mechanistic studies indicated that ghrelin treatment inhibited the high glucose-induced increase in FDX1 gene expression(all P<0.05).MeRIP-qPCR analysis further demonstrated that ghrelin treatment re-duced the m6A modification level at the 820th site of FDX1-mRNA induced by high glucose(P<0.05).Conclusions The high glucose environment induces cuproptosis in HRMECs,leading to decreased cell viability.Ghrelin exerts a protective effect on HRMECs by reducing the m6A modification level of FDX1-mRNA,thereby inhibiting copper-induced cell death.关键词
胃饥饿素/铜死亡/N6-甲基腺苷修饰/糖尿病视网膜病变/高糖/视网膜血管内皮细胞/细胞培养Key words
Ghrelin/Cuproptosis/N6-methyladenosine modification/Diabetic retinopathy/High glucose/Retina vascular endothelial cell/Cell culture引用本文复制引用
关小荣,张进,李蓉..胃饥饿素对高糖诱导的视网膜血管内皮细胞铜死亡的影响[J].临床眼科杂志,2026,34(2):97-103,7.基金项目
四川省卫健委科研项目(24WXXT13) （24WXXT13）
中国研究型医院学会眼科新技术孵化项目(Y2025FH-YKYSJSJ07-18) （Y2025FH-YKYSJSJ07-18）
