Effect of acetyl L-carnitine on human retinal pigment epithelium-19 cells in hypoxic conditions  

乙酰左旋肉碱在缺氧条件下对人视网膜色素上皮-19细胞的影响

作　　者：Ali Dal Onur Catak Murat Erdag Mehmet Canleblebici Ebru Onalan Ilay Buran Ali Dal;Onur Catak;Murat Erdag;Mehmet Canleblebici;Ebru Onalan;Ilay Buran(Firat大学医学院眼科,土耳其埃拉泽23119;穆斯塔法凯末尔大学Ata Sokmen医学院眼科,土耳其哈塔伊31100;土耳其开塞利州立医院眼科,38200;Firat大学医学院医学生物学系,土耳其埃拉泽23100)

机构地区：[1]Department of Ophthalmology,Faculty of Medicine,Firat University,Elazig 23119,Turkey [2]Department of Ophthalmology,Ata Sokmen Faculty of Medicine,Mustafa Kemal University,Hatay 31100,Turkey [3]Department of Ophthalmology,Kayseri State Hospital,Kayseri 38200,Turkey [4]Department of Medical Biology,Faculty of Medicine,Firat University,Elazig 23100,Turkey

出　　处：《国际眼科杂志》2024年第10期1515-1521,共7页International Eye Science

基　　金：Firat大学科研中心项目(No.TF:19.41)。

摘　　要：AIM:To investigate the effect of acetyl-L-carnitine(ALCAR)on cell viability,morphological integrity,and vascular endothelial growth factor(VEGF)expression in human retinal pigment epithelium(ARPE-19)cells using a hypoxic model.METHODS:In the first set of experiments,the optimal CoCl_(2) dose was determined by exposing ARPE-19 cell cultures to different concentrations.To evaluate the effect of ALCAR on cell viability,five groups of ARPE-19 cell culture were established that included a control group,a sham group(200μM CoCl_(2)),and groups that received 1,10 and 100 mM doses of ALCAR combined with 200μM CoCl_(2),respectively.The cell viability was measured by MTT assay.The morphological characteristics of cells were observed by an inverted phase contrast microscope.The levels of VEGF and HIF-1α secretion by ARPE-19 cells were detected by enzyme linked immunosorbent assay(ELISA)assay.RESULTS:ARPE-19 cells were exposed to different doses of CoCl_(2) in order to create a hypoxia model.Nevertheless,when exposed to a concentration of 200μM CoCl_(2),a notable decrease in viability to 83% was noted.ALCAR was found to increase the cell viability at 1 mM and 10 mM concentrations,while the highest concentration(100 mM)did not have an added effect.The cell viability was found to be significantly higher in the groups treated with a concentration of 1 mM and 10 mM ALCAR compared to the Sham group(P=0.041,P=0.019,respectively).The cell viability and morphology remained unaffected by the greatest dose of ALCAR(100 mM).The administration of 10 mM ALCAR demonstrated a statistically significant reduction in the levels of VEGF and HIF-1α compared with the Sham group(P=0.013,P=0.033,respectively).CONCLUSION:The findings from the current study indicate that ALCAR could represent a viable therapeutic option with the potential to open up novel treatment pathways for retinal diseases,particular relevance for age-related macular degeneration(AMD).However,to fully elucidate ALCAR’s application potential in retinal diseases,additional 目的:使用缺氧模型探究乙酰左旋肉碱(ALCAR)对人视网膜色素上皮(ARPE-19)细胞活力、形态完整性和血管内皮生长因子(VEGF)表达的影响。方法:第一组实验通过暴露ARPE-19细胞培养物于不同浓度确定最佳CoCl_(2)剂量。建立五组ARPE-19细胞培养物,包括对照组,假手术组(200μM CoCl_(2))和分别接受1、10、100 mM ALCAR联合200μM CoCl_(2)组,以评估ALCAR对细胞活力的影响。使用MTT法测量细胞活力。通过倒置相差显微镜观察细胞的形态特征。采用酶联免疫吸附实验(ELISA)检测ARPE-19细胞分泌VEGF和HIF-1α的水平。结果:ARPE-19细胞暴露于不同剂量的CoCl_(2)中,以创建缺氧模型。然而,暴露于浓度为200μM CoCl_(2)时,细胞活力显著降低至83%。ALCAR在1 mM和10 mM浓度下可增加细胞活力,而最大浓度(100 mM)没有额外效果。与假手术组相比,浓度为1 mM和10 mM ALCAR组的细胞活力显著更高(P=0.041、0.019)。细胞活力和形态不受最大剂量ALCAR(100 mM)的影响。与假手术组相比,10 mM ALCAR组VEGF和HIF-1α水平显著降低(P=0.013、0.033)。结论:ALCAR是可行的治疗选择,可为视网膜疾病开辟新的治疗途径,与年龄相关性黄斑变性(AMD)特别相关。然而,仍需开展进一步研究明确定义其确切机制,以期充分阐明ALCAR对抗视网膜疾病的应用潜力。

关 键 词：acetyl-L-carnitine(ALCAR) human retinal pigment epithelium(ARPE-19) vascular endothelial growth factor(VEGF) hypoxia-inducible factor 1(HIF-1α) 

分 类 号：R774.1[医药卫生—眼科]