Diabetes can aggravate myocardial ischemia/reperfusion injury (MIRI), but the role of long non-coding RNA H19 (lncRNA H19) is still unclear. The purpose of this study was to investigate the effect of lncRNA H19 on MIRI in diabetic mice. C57BL/KsJ db/db diabetes mice and db/+ normal mice (n = 40/group) were divided into sham operation, ischemia/reperfusion (I/R), and I/R+Lv-H19 (lentivirus-mediated H19 overexpression) groups. Echocardiography evaluation of cardiac function and Evans Blue/triphenyltetrazolium chloride staining were used to determine the infarct area; terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and caspase-3 to detect cell apoptosis; western blot to detect autophagy markers (LC3-II/I, p62) and HIF-1α protein expression; and dual luciferase reporter genes to validate the competitive endogenous RNA (ceRNA) mechanism. H19 expression in the hearts of diabetic mice after I/R was significantly lower than that of normal mice (P < 0.05). H19 overexpression significantly improved cardiac function (left ventricular ejection fraction and fractional shortening restored to near-normal levels), reduced infarct size, and lowered serum CK, CK-MB, and LDH levels (P < 0.05). H19 overexpression regulated autophagic flow (LC3-II/I ratio and p62 expression reversal) and inhibited caspase-3 activity (P < 0.05). Mechanistically, H19 acts as a ceRNA for miR-4735-3p, releasing its inhibition of hypoxia-inducible factor 1 alpha (HIF-1α) and activating the HIF-1α signaling pathway. The results of this study provide mechanistic insight into the molecular processes underlying myocardial I/R injury in diabetic mice and identify LNCRNA H19 as a candidate target for further preclinical research.
