Original Article
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World J Gastroenterol. Nov 21, 2010; 16(43): 5424-5434
Published online Nov 21, 2010. doi: 10.3748/wjg.v16.i43.5424
Endogenous leptin fluctuates in hepatic ischemia/reperfusion injury and represents a potential therapeutic target
Ji Lin, Xiao-Ning Gao, Guang-Tao Yan, Hui Xue, Xiu-Hua Hao, Lu-Huan Wang
Ji Lin, Guang-Tao Yan, Hui Xue, Xiu-Hua Hao, Lu-Huan Wang, Research Laboratory of Biochemistry, Basic Medical Institute, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China
Xiao-Ning Gao, Department of Hematology, Clinical Division of Internal Medicine, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China
Author contributions: Lin J and Gao XN contributed equally to this work; Lin J and Yan GT designed the research; Xue H and Hao XH prepared leptin antibody and iodinated leptin; Lin J and Wang LH measured the serum variables; Lin J and Gao XN performed the histological evaluation and immunohistochemistry; Lin J, Gao XN and Yan GT analyzed the data and wrote the manuscript.
Supported by National Natural Science Foundation of China, No. 30670821; National Key Technology R&D Program, No. 2006BAF07B01; Special Funds for Key Program of Public Welfare of National Ministry of Science and Technology, No. 2002D1A40019; and Nursery Fund of Chinese PLA General Hospital, No. 06MP83
Correspondence to: Guang-Tao Yan, Professor, Research Laboratory of Biochemistry, Basic Medical Institute, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China. yan301@263.net
Telephone: +86-10-66937072 Fax: +86-10-68176512
Received: August 10, 2010
Revised: September 13, 2010
Accepted: September 20, 2010
Published online: November 21, 2010
Abstract

AIM: To evaluate the role of leptin in the internal disorders during hepatic ischemia/reperfusion injury.

METHODS: A rat model of 70% hepatic ischemia/reperfusion injury was established, with groups of sham-operation (Sham), 60 min ischemia/60 min reperfusion (I60’R60’), I60’R150’, I60’R240’ and I60’R360’. Serum leptin was detected by a self-produced radioimmunoassay; serum glucose, total anti-oxidation capacity, myeloperoxidase, alanine transaminase and diamine oxidase were determined by relevant kits, while histological alterations and protein levels of leptin in the lung, liver and duodenum were examined by hematoxylin-eosin staining and immunohistochemistry. Spearman’s rank correlation between leptin and other variables or grading of tissue impairment were analyzed simultaneously.

RESULTS: Serum leptin in I60’R360’ was significantly higher than in Sham and I60’R240’ groups (both P < 0.05), serum glucose in I60’R360’ was higher than in Sham and I60’R150’ (both P < 0.05), and serum total anti-oxidation capacity in I60’R240’ and I60’R360’ were higher than in Sham (both P < 0.05) and I60’R150’groups (both P < 0.01). Serum myeloperoxidase in groups of I60’R240’ and I60’R360’ were lower than in I60’R150’group (both P < 0.05), serum alanine transaminase in the four reperfusion groups were higher than in the Sham group (all P < 0.05), while serum DAO in I60’R360’ was lower than in I60’R60’ (P < 0.05). Histological impairment in the lung, liver and duodenum at the early phase of this injury was more serious, but the impairment at the later phase was lessened gradually. Protein levels of leptin in the lung in the four reperfusion groups were significantly lower than in the Sham group (all P < 0.01), decreasing in the order of I60’R150’, I60’R60’, I60’R360’ and I60’R240’; the levels in the liver in I60’R60’ and I60’R240’ were higher than in the Sham group (both P < 0.01), while the levels in I60’R240’ and I60’R360’ were lower than in I60’R60’ (both P < 0.01); the levels in duodenum in I60’R240’ and I60’R360’ were higher than in Sham, I60’R60’ and I60’R150’ (all P < 0.01), while the level in I60’R150’ was lower than in I60’R60’ (P < 0.05). There was a significantly positive correlation between serum leptin and alanine transaminase (ρ = 0.344, P = 0.021), a significantly negative correlation between the protein level of leptin in the lung and its damage scores (ρ = -0.313, P = 0.036), and a significantly positive correlation between the protein level of leptin in the liver and its damage scores (ρ = 0.297, P = 0.047).

CONCLUSION: Endogenous leptin fluctuates in hepatic ischemia/reperfusion injury, exerts a potency to rehabilitate the internal disorders and represents a potential target for supportive therapy.

Keywords: Leptin; Reperfusion injury; Liver; Lung; Duodenum; Recovery of function