Apigenin attenuates myocardial ischemia-reperfusion injury through miR-۴۴۸/SIRT۱ axis

Objective(s): Myocardial ischemia/reperfusion injury (MIRI) is the primary pathological injury following ischemic cardiomyocyte therapy, but there are few effective treatments available for MIRI. Apigenin (API) is an active ingredient of herbal medicine. Our study aims to verify whether API regulates autophagy and apoptosis against MIRI via miR-۴۴۸/Sirtuin-۱ (SIRT۱) axis.Materials and Methods: MTT, SOD, and LDH assays were used to measure cell viability, oxidative stress injury, and cell damage, respectively. RT-qPCR, western blot, and ELISA were used to measure RNA and protein expression levels.Results: Compared with the control group, cell viability and SOD levels in the cells of the OGD/R group were significantly decreased, LDH release in the cells was significantly increased, the level of miR-۴۴۸ in the cells was significantly increased, the levels of SIRT۱ mRNA and protein in the cells were significantly increased, the expression of LCII/I and Bcl-۲ proteins in the cells were significantly down-regulated, and the expression of p۶۲, Bax proteins in the cells and caspase-۳ protein in the cell supernatant were significantly up-regulated. Compared with the OGD/R group, the above indicators were significantly reversed in the OGD/R+API group and the OGD/R+miR-۴۴۸ inhibitor group. Compared to the OGD/R+miR-۴۴۸ inhibitor group, the above indicators were significantly reversed in the OGD/R+miR-۴۴۸ inhibitor+EX۵۲۷ (SIRT۱ inhibitor) group. Compared to the OGD/R+API group, the above indicators were significantly reversed in the OGD/R+API+miR-۴۴۸ mimic group, OGD/R+API+EX۵۲۷ group, and OGD/R+API+CA-۵f (autophagy inhibitor) group.Conclusion: API regulates autophagy and apoptosis via the miR-۴۴۸/SIRT۱ axis against MIRI.

کلیدواژه ها:

Apigenin ، Apoptosis ، Autophagy ، MiR-۴۴۸ ، OGD/R