The Role of miR-34a in the Hepatoprotective Effect of Hydrogen Sulfide on Ischemia/Reperfusion Injury in Young and Old Rats

Hydrogen sulfide (H(2)S) can protect the liver against ischemia-reperfusion (I/R) injury. However, it is unknown whether H(2)S plays a role in the protection of hepatic I/R injury in both young and old patients. This study compared the protective effects of H(2)S in a rat model (young and old animals) of I/R injury and the mechanism underlying its effects. Young and old rats were assessed following an injection of NaHS. NaHS alone reduced hepatic I/R injury in the young rats by activating the nuclear erythroid-related factor 2 (Nrf2) signaling pathway, but it had little effect on the old rats. NaHS pretreatment decreased miR-34a expression in the hepatocytes of the young rats with hepatic I/R. Overexpresion of miR-34a decreased Nrf-2 and its downstream target expression, impairing the hepatoprotective effect of H(2)S on the young rats. More importantly, downregulation of miR-34a expression increased Nrf-2 and the expression of its downstream targets, enhancing the effect of H(2)S on hepatic I/R injury in the old rats. This study reveals the different effects of H(2)S on hepatic I/R injury in young and old rats and sheds light on the involvement of H(2)S in miR-34a modulation of the Nrf-2 pathway.