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

被引：71

作者：

Huang, Xinli ^{[1
]}

Gao, Yun ^{[1
]}

Qin, Jianjie ^{[1
]}

Lu, Sen ^{[1
]}

机构：

[1] Nanjing Med Univ, Affiliated Hosp 1, Ctr Liver Transplantat, Key Lab Living Donor Liver Transplantat,Minist Hl, Nanjing, Jiangsu, Peoples R China

来源：

PLOS ONE | 2014年 / 9卷 / 11期

关键词：

ISCHEMIA-REPERFUSION INJURY; SIGNALING MOLECULE; LIVER; MICRORNAS; NRF2; PATHWAY; DEATH;

D O I：

10.1371/journal.pone.0113305

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Hydrogen sulfide (H2S) can protect the liver against ischemia-reperfusion (I/R) injury. However, it is unknown whether H2S plays a role in the protection of hepatic I/R injury in both young and old patients. This study compared the protective effects of H2S 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 H2S 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 H2S on hepatic I/R injury in the old rats. This study reveals the different effects of H2S on hepatic I/R injury in young and old rats and sheds light on the involvement of H2S in miR-34a modulation of the Nrf-2 pathway.

引用

页数：10