Myocardial ischemia/reperfusion injury (MIRI) causes severe damage in cardiac tissue,
thereby resulting in a high rate of mortality. 6-Gingerol (6-G) is reported to play
an essential role in alleviating MIRI. However, the underlying mechanism remains obscure.
This study was intended to explore the potential mechanism by which 6-G functions.
Q-PCR was employed to quantify the relative RNA levels of long noncoding RNA (lncRNA)
H19 (H19), miR-143, and ATG7, an enzyme essential for autophagy, in HL-1 cells. Western
blotting, immunofluorescence, and immunohistochemistry were employed for protein evaluation
in cultured cells or mouse tissues. Cell viability, cytotoxicity, and apoptosis were
analysed by CCK-8, LDH, and flow cytometry assays, respectively. The binding sites
for miR-143 were predicted using starBase software and experimentally validated through
a dual-luciferase reporter system. Here, we found that 6-G elevated cellular H19 expression
in hypoxia/reoxygenation (H/R)-treated HL-1 cells. Moreover, 6-G increased Bcl-2 expression
but reduced cleaved caspase 3 and caspase 9 protein levels. Mechanistically, H19 directly
interacted with miR-143 and lowered its cellular abundance by acting as a molecular
sponge. Importantly, ATG7 was validated as a regulated gene of miR-143, and the depletion
of miR-143 by H19 caused an increased in ATG7 expression, which in turn promoted the
autophagy process. Last, mouse experiments highly supported our in vitro findings
that 6-G relieves MIRI by enhancing autophagy. The H19/miR-143/ATG7 axis was shown
to be critical for the function of 6-G in relieving MIRI.