Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Apr 21, 2012; 18(15): 1765-1772
Published online Apr 21, 2012. doi: 10.3748/wjg.v18.i15.1765
Diazoxide attenuates ischemia/reperfusion injury via upregulation of heme oxygenase-1 after liver transplantation in rats
Zhong Zeng, Han-Fei Huang, Fei He, Lin-Xi Wu, Jie Lin, Ming-Qing Chen
Zhong Zeng, Han-Fei Huang, Fei He, Lin-Xi Wu, Jie Lin, Ming-Qing Chen, Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical College, Kunming 650032, Yunnan Province, China
Author contributions: Zeng Z and Huang HF contributed equally to this work; Zeng Z, Huang HF and Chen MQ designed the research; Huang HF, He F, Wu LX and Lin J performed the research; Zeng Z and Chen MQ contributed analytic tools; He F analyzed the data; Zeng Z and Huang HF wrote the paper.
Supported by Social Development Projects of Yunnan Province, No. 2008CA026
Correspondence to: Ming-Qing Chen, MD, Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical College, 295 Xichang Road, Kunming 650032, Yunnan Province, China. kmchenmingqing@163.com
Telephone: +86-871-5359202 Fax: +86-871-5359202
Received: October 11, 2011
Revised: January 17, 2012
Accepted: April 9, 2012
Published online: April 21, 2012
Abstract

AIM: To evaluate the effects of diazoxide on ischemia/reperfusion (I/R)-injured hepatocytes and further elucidate its underlying mechanisms.

METHODS: Male Sprague-Dawley rats were randomized (8 for donor and recipient per group) into five groups: I/R group (4 h of liver cold ischemia followed by 6 h of reperfusion); heme oxygenase-1 (HO-1) small interfering RNA (siRNA) group (injection of siRNA via donor portal vein 48 h prior to harvest); diazoxide (DZ) group (injection of DZ via donor portal vein 10 min prior to harvest); HO-1 siRNA + DZ group; and siRNA control group. Blood and liver samples were collected at 6 h after reperfusion. The mRNA expressions and protein levels of HO-1 were determined by reverse transcription polymerase chain reaction and Western blotting, and tissue morphology was examined by light and transmission electron microscopy. Serum transaminases level and cytokines concentration were also measured.

RESULTS: We observed that a significant reduction of HO-1 mRNA and protein levels in HO-1 siRNA and HO-1 siRNA + DZ group when compared with I/R group, while the increases were prominent in the DZ group. Light and transmission electron microscopy indicated severe disruption of tissue with lobular distortion and mitochondrial cristae damage in the HO-1 siRNA and HO-1 siRNA + DZ groups compared with DZ group. Serum alanine aminotransferase, aspartate transaminase, tumor necrosis factor-α and interleukin-6 levels increased in the HO-1 siRNA and HO-1 siRNA + DZ groups, and decreased in the DZ group.

CONCLUSION: The protective effect of DZ may be induced by upregulation of HO-1. By inhibiting expression of HO-1, this protection pretreated with DZ was abolished.

Keywords: Ischemia/reperfusion injury, Diazoxide, Heme oxygenase-1, Liver transplantation, Rat