Melatonin prevents hemorrhagic shock-induced liver injury in rats through an Akt-dependent HO-1 pathway

作者：Hsu Jun Te^*; Kuo Chia Jung; Chen Tsung Hsing; Wang Frank; Lin Chun Jun; Yeh Ta Sen; Hwang Tsann Long; Jan Yi Yin

来源：Journal of Pineal Research, 2012, 53(4): 410-416.

DOI：10.1111/j.1600-079X.2012.01011.x

• Akt
• hemorrhagic shock
• HO-1
• inflammation
• liver injury
• melatonin

Although melatonin treatment following trauma-hemorrhage or ischemic reperfusion prevents organs from dysfunction and injury, the precise mechanism remains unknown. This study tested whether melatonin prevents liver injury following trauma-hemorrhage involved the protein kinase B (Akt)-dependent heme oxygenase (HO)-1 pathway. After a 5-cm midline laparotomy, male rats underwent hemorrhagic shock (mean blood pressure approximately 40 mmHg for 90 min) followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle, melatonin (2 mg/kg), or melatonin plus phosphoinositide 3-kinase (PI3K) inhibitor wortmannin (1 mg/kg). At 2 hr after trauma-hemorrhage, the liver tissue myeloperoxidase activity, malondialdehyde, adenosine triphosphate, serum alanine aminotransferase, and aspartate aminotransferase levels were significantly increased compared with sham-operated control. Trauma-hemorrhage resulted in a significant decrease in the Akt activation in comparison with the shams (relative density, 0.526 +/- 0.031 versus 1.012 +/- 0.066). Administration of melatonin following trauma-hemorrhage normalized liver Akt phosphorylation (0.993 +/- 0.061), further increased mammalian target of rapamycin (mTOR) activation (5.263 +/- 0.338 versus 2.556 +/- 0.225) and HO-1 expression (5.285 +/- 0.325 versus 2.546 +/- 0.262), and reduced cleaved caspase-3 levels (2.155 +/- 0.297 versus 5.166 +/- 0.309). Coadministration of wortmannin abolished the melatonin-mediated attenuation of the shock-induced liver injury markers. Our results collectively suggest that melatonin prevents hemorrhagic shock-induced liver injury in rats through an Akt-dependent HO-1 pathway.

• 出版日期2012-11
• 单位长春大学