Adenoviral Gene Transfer of Hepatic Stimulator Substance Confers Resistance Against Hepatic Ischemia-Reperfusion Injury by Improving Mitochondrial Function

作者：Jiang, Shu-Jun; Li, Wen; An, Wei^*

来源：Human Gene Therapy, 2013, 24(4): 443-456.

DOI：10.1089/hum.2012.219

• H2O2-INDUCED CELL APOPTOSIS
• LIVER-REGENERATION ALR
• ISCHEMIA/REPERFUSION INJURY
• PERMEABILITY TRANSITION
• REACTIVE OXYGEN
• SULFHYDRYL OXIDASE
• RAT-LIVER
• AUGMENTOR
• EXPRESSION
• HEPATOCYTES

Hepatic stimulator substance (HSS) has been suggested to protect liver cells from various toxins. However, the precise role of HSS in hepatic ischemia-reperfusion (I/R) injury remains unknown. This study aims to elucidate whether overexpression of HSS could attenuate hepatic ischemia-reperfusion injury and its possible mechanisms. Both in vivo hepatic I/R injury in mice and in vitro hypoxia-reoxygenation (H/R) in a cell model were used to evaluate the effect of HSS protection after adenoviral gene transfer. Moreover, a possible mitochondrial mechanism of HSS protection was investigated. Efficient transfer of the HSS gene into liver inhibited hepatic I/R injury in mice, as evidenced by improvement in liver function tests, the preservation of hepatic morphology, and a reduction in hepatocyte apoptosis. HSS overexpression also inhibited H/R-induced cell death, as detected by cell viability and cell apoptosis assays. The underlying mechanism of this hepatic protection might involve the attenuation of mitochondrial dysfunction and mitochondrial-dependent cell apoptosis, as shown by the good preservation of mitochondrial ultrastructure, mitochondrial membrane potential, and the inhibition of cytochrome c leakage and caspase activity. Moreover, the suppression of H/R-induced mitochondrial ROS production and the maintenance of mitochondrial respiratory chain complex activities may participate in this mechanism. This new function of HSS expands the possibility of its application for the prevention of I/R injury, such as hepatic resection and liver transplantation in clinical practice.

• 出版日期2013-4
• 单位首都医科大学