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Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Jul 28, 2008; 14(28): 4546-4550
Published online Jul 28, 2008. doi: 10.3748/wjg.14.4546
Delayed ethyl pyruvate therapy attenuates experimental severe acute pancreatitis via reduced serum high mobility group box 1 levels in rats
Zhi-Yong Yang, Yan Ling, Tao Yin, Jing Tao, Jiong-Xin Xiong, He-Shui Wu, Chun-You Wang
Zhi-Yong Yang, Yan Ling, Tao Yin, Jing Tao, Jiong-Xin Xiong, He-Shui Wu, Chun-You Wang, Department of Pancreatic Surgery, Xiehe Hospital, Tongji Medical College, Huazhong University of Sciecne and Technology, Wuhan 430022, Hubei Province, China
Author contributions: Yang ZY and Ling Y contributed equally to this work; Yang ZY, Ling Y, Xiong JX, Wu HS and Wang CY designed research; Yang ZY, Ling Y and Tao J performed research; Yang ZY, Ling Y and Yin T wrote the paper.
Correspondence to: Chun-You Wang, Department of Pancreatic Surgery, Xiehe Hospital, Tongji Medical College, Huazhong University of Sciecne and Technology, 1277 Jiefang Road, Wuhan 430022, Hubei Province, China. dryzy@163.com
Telephone: +86-27-85351621
Fax: +86-27-85351673
Received: April 18, 2008
Revised: June 16, 2008
Accepted: June 23, 2008
Published online: July 28, 2008
Abstract

AIM: To investigate the effect of delayed ethyl pyruvate (EP) delivery on distant organ injury, survival time and serum high mobility group box 1 (HMGB1) levels in rats with experimental severe acute pancreatitis (SAP).

METHODS: A SAP model was induced by retrograde injection of artificial bile into the pancreatic ducts of rats. Animals were divided randomly into three groups (n = 32 in each group): sham group, SAP group and delayed EP treatment group. The rats in the delayed EP treatment group received EP (30 mg/kg) at 12 h, 18 h and 30 h after induction of SAP. Animals were sacrificed, and samples were obtained at 24 h and 48 h after induction of SAP. Serum HMGB1, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine (Cr) levels were measured. Lung wet-to-dry-weight (W/D) ratios and histological scores were calculated to evaluate lung injury. Additional experiments were performed between SAP and delayed EP treatment groups to study the influence of EP on survival times of SAP rats.

RESULTS: Delayed EP treatment significantly reduced serum HMGB1 levels, and protected against liver, renal and lung injury with reduced lung W/D ratios (8.22 ± 0.42 vs 9.76 ± 0.45, P < 0.01), pulmonary histological scores (7.1 ± 0.7 vs 8.4 ± 1.1, P < 0.01), serum AST (667 ± 103 vs 1 368 ± 271, P < 0.01), ALT (446 ± 91 vs 653 ± 98, P < 0.01) and Cr (1.2 ± 0.3 vs 1.8 ± 0.3, P < 0.01) levels. SAP rats had a median survival time of 44 h. Delayed EP treatment significantly prolonged median survival time to 72 h (P < 0.01).

CONCLUSION: Delayed EP therapy protects against distant organ injury and prolongs survival time via reduced serum HMGB1levels in rats with experimental SAP. EP may potentially serve as an effective new therapeutic option against the inflammatory response and multiple organ dysfunction syndrome (MODS) in SAP patients.

Keywords: Severe acute pancreatitis; Ethyl pyruvate; High mobility group box 1; Multiple organ dysfunction syndrome; Survival time