Basic Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Mar 7, 2006; 12(9): 1373-1378
Published online Mar 7, 2006. doi: 10.3748/wjg.v12.i9.1373
Alanyl-glutamine dipeptide inhibits hepatic ischemia-reperfusion injury in rats
Chang-Jun Jia, Chao-Liu Dai, Xu Zhang, Kai Cui, Feng Xu, Yong-Qing Xu
Chang-Jun Jia, Chao-Liu Dai, Xu Zhang, Feng Xu, Yong-Qing Xu, Department of Hepatobiliary Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning Province, China
Kai Cui, Department of General Surgery, Fengtian Hospital, Shenyang Medical University, Shenyang 110024, Liaoning Province, China
Supported by the Natural Science Foundation of Liaoning Province, No. 20022063
Correspondence to: Professor Chao-Liu Dai, Department of Hepatobiliary Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning Province, China. daicl-sy@tom.com
Telephone: +86-24-83955232 Fax: +86-24-83955092
Received: August 31, 2005
Revised: October 1, 2005
Accepted: October 10, 2005
Published online: March 7, 2006
Abstract

AIM: To investigate the protective effect and mechanism of alanyl-glutamine dipeptide (Ala-Gln) against hepatic ischemia-reperfusion injury in rats.

METHODS: Rats were divided into group C as normal control Group (n=16) and group G as alanyl-glutamine pretreatment (n=16). Rats were intravenously infused with 0.9% saline solution in group C and Ala-Gln -enriched (2% glutamine) 0.9% saline solution in group G via central venous catheter for three days. Then all rats underwent hepatic warm ischemia for 30 min followed by different periods of reperfusion. Changes in biochemical parameters, the content of glutathione (GSH) and the activity of superoxide dismutase (SOD) in liver tissue, Bcl-2 and Bax protein expression and morphological changes of liver tissue were compared between both groups.

RESULTS: One hour after reperfusion, the levels of liver enzymes in group G were significantly lower than those in group C (P<0.05). Twenty-four hours after reperfusion, the levels of liver enzymes in both groups were markedly recovered and the levels of liver enzyme in group G were also significantly lower than those in group C (P <0.01). One and 24 h after reperfusion, GSH content in group G was significantly higher than that in group C (P <0.05). There was no statistical difference in activities of SOD between the two groups. One and 24 h after reperfusion, the positive expression rate of Bcl-2 protein was higher in group G than in group C (P <0.05) and the positive expression rate of Bax protein was lower in group G than in group C (P < 0.05). Histological and ultrastructural changes of liver tissue were inhibited in group C compared to group G.

CONCLUSION: Our results suggest that Ala-Gln pretreatment provides the rat liver with significant tolerance to warm ischemia-reperfusion injury, which may be mediated partially by enhancing GSH content and regulating the expression of Bcl-2 and Bax proteins in the liver tissue.

Keywords: Alanyl-glutamine dipeptide; Hepatic ischemia-reperfusion injury; Glutathione; Bcl-2; Bax