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CoCl₂剂量。建立五组ARPE-19细胞培养物，包括对照组，假手术组(200 μM CoCl₂)和分别接受1、10、100 mM ALCAR联合200 μM CoCl₂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CoCl₂中，以创建缺氧模型。然而，暴露于浓度为200 μM CoCl₂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。

METHODS: In the first set of experiments, the optimal CoCl₂ 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(200 μM CoCl₂), and groups that received 1, 10 and 100 mM doses of ALCAR combined with 200 μM CoCl₂, 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 CoCl₂ in order to create a hypoxia model. Nevertheless, when exposed to a concentration of 200 μM CoCl₂, 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 investigation is necessary to clearly define the exact mechanisms involved.