Objective: To investigate the effect and mechanism of long non-coding RNA RMRP(LncRNA RMRP) on oxygen-glucose deprivation/reperfusion(OGD/R)-induced ferroptosis in mouse HL-1 cardiomyocytes by regulating miR-766-5p. Methods: HL-1 cells were cultured in vitro, and OGD/R models were established. The expression levels of LncRNA RMRP in HL-1 cells at various reperfusion time points were subsequently quantified using qRT-PCR. The LncRNA RMRP small RNA interference fragment(si-RMRP) and its corresponding negative control(si-NC), as well as the miR-766-5p inhibitor and its respective negative control(inhibitor-NC), were transfected into HL-1 cells. Subsequently, the cells were subjected to OGD/R treatment. CCK-8 assay was employed to evaluate cell viability. Assay kits were employed to measure the levels of lactate dehydrogenase(LDH) in the cell supernatant, as well as the intracellular levels of malondialdehyde(MDA), superoxide dismutase(SOD), glutathione(GSH), and ferrous ion(Fe2+). qRT-PCR analysis was conducted to assess the expression levels of LncRNA RMRP and miR-766-5p. Western blot analysis was conducted to assess the expression levels of proteins associated with ferroptosis including GPX4, SLC7A11, and FTH1. Dual-luciferase reporter assays were performed to investigate the sponge adsorption relationship between LncRNA RMRP and miR-766-5p. Results: As reperfusion time extended, the expression level of LncRNA RMRP in cells progressively increased(P2+ levels within the cells, and decreased the activities of SOD and GSH in cells(P2+ levels within the cells, and promoting SOD and GSH activities in cells(PP < 0. 01) . Furthermore , silencing LncRNA RMRP upregulated the protein expression levels of GPX4 , SLC7A11 , and FTH1(P < 0. 01) . The dual-luciferase reporter assay confirmed that LncRNA RMRP could regulate the expression of miR-766- 5p through a sponge adsorption mechanism. Partial inhibition of miR-766-5p inhibitor expression could mitigate the improvement effect caused by LncRNA RMRP silencing on OGD/R-induced ferroptosis in HL-1 cells. Conclusion Silencing LncRNA RMRP inhibits OGD/R-induced ferroptosis in HL-1 cells , potentially through the sponge-mediated regulation of miR-766-5p expression.

Photodynamic therapy, a new type of non-invasive treatment, is based on the principle that the photosensitizer excited by laser can transfer energy to oxygen, which generates cytotoxic singlet oxygen and thus induce tumor cell apoptosis or necrosis. As an oxygen-dependent therapy, the antitumor effect of photodynamic therapy is obviously limited by hypoxia environment of solid tumor tissue. Therefore, reversing and improving the hypoxia of tumor tissue can significantly enhance the efficacy of photodynamic therapy. This review focuses on the progress of tumor oxygenation strategy mediated by nano-delivery system, including direct oxygen delivery strategies, catalytic oxygen production strategies, responsive material in situ oxygen supply strategies and microorganism oxygen supply strategies, aiming to improve the antitumor effect of photodynamic therapy. It provides new ideas and new approaches for further study of oxygen-enchancing nano-delivery system for photodynamic therapy.

10.3969/j.issn.1000-3606.2013.06.018