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World J Gastroenterol. Nov 7, 2007; 13(41): 5506-5511
Published online Nov 7, 2007. doi: 10.3748/wjg.v13.i41.5506
Effects of large dose of dexamethasone on inflammatory mediators and pancreatic cell apoptosis of rats with severe acute pancreatitis
Xi-Ping Zhang, Li Chen, Qi-Fang Hu, Hua Tian, Ru-Jun Xu, Zhi-Wei Wang, Ke-Yi Wang, Qi-Hui Cheng, Wei Yan, Yun Li, Qing-Yu Li, Qing He, Fei Wang
Xi-Ping Zhang, Department of General Surgery, Hangzhou First People's Hospital, Hangzhou 310006, Zhejiang Province, China
Li Chen, Hua Tian, Department of General Surgery, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
Qi-Fang Hu, Zhejiang Traditional Chinese Medicine University, Hangzhou 310053, Zhejiang Province, China
Ru-Jun Xu, Department of Pathology, Hangzhou First People's Hospital, Hangzhou 310006, Zhejiang Province, China
Zhi-Wei Wang, Ke-Yi Wang, Central Lab, Hangzhou First People's Hospital, Hangzhou 310006, Zhejiang Province, China
Qi-Hui Cheng, Department of Gynaecology and Obstetrics, Hangzhou First People's Hospital, Hangzhou 310006, Zhejiang Province, China
Wei Yan, Yun Li, Qing-Yu Li, Qing He, Fei Wang, Manufacturing Laboratory, Hangzhou First People's Hospital, Hangzhou 310006, Zhejiang Province, China
Author contributions: All authors contributed equally to the work.
Supported by Grants for Traditional Chinese Medicine Science of Zhejiang Province, and Medical Science and Technology of Zhejiang Province and Hangzhou
Correspondence to: Xi-Ping Zhang MD, Department of General Surgery, Hangzhou First People's Hospital, 261 Huansha Road, Hangzhou 310006, Zhejiang Province, China. zxp99688@vip.163.com
Telephone: +86-571-87065701 Fax: +86-571-87914773
Received: June 28, 2007
Revised: August 17, 2007
Accepted: August 30, 2007
Published online: November 7, 2007
Abstract

AIM: To investigate the influence of high dose of dexamethasone on inflammatory mediators and apoptosis of rats with severe acute pancreatitis (SAP).

METHODS: SAP rats were randomly assigned to the model group and treatment group while the normal rats were assigned to the sham operation group. The mortality, ascite volumes, ascites/body weight ratio and pancreas pathological changes of all rats were observed at 3, 6 and 12 h after operation. Their contents of amylase and endotoxin in plasma and contents of tumor necrosis factor (TNF-α), phospholipase A2 (PLA2) and IL-6 in serum were also determined. The microarray sections of their pancreatic tissues were prepared, terminal transferase dUTP nick end labeling (TUNEL) staining was performed and apoptotic indexes were calculated.

RESULTS: There was no marked difference between treatment group and model group in survival. The contents of amylase and endotoxin in plasma and contents of TNF-α, PLA2 and IL-6 in serum, ascite volumes, ascites/body weight ratio and pancreas pathological scores were all lower in treatment group than in model group to different extents at different time points [P < 0.05, 58.3 (26.4) ng/L vs 77.535 (42.157) ng/L in TNF-α content, 8.00 (2.00) points vs 9.00 (2.00) points in pathological score of pancreas respectively; P < 0.01, 0.042 (0.018) EU/mL vs 0.056 (0.0195) EU/mL in endotoxin content, 7791 (1863) U/L vs 9195 (1298) U/L in plasma amylase content, 1.53 (0.79) vs 2.38 (1.10) in ascites/body weight ratio, 8.00 (1.00) points vs 11.00 (1.50) points in pathological score of pancreas; P < 0.001, 3.36 (1.56) ng/L vs 5.65 (1.08) ng/L in IL-6 content, 4.50 (2.00) vs 7.20 (2.00), 4.20 (1.60) vs 6.40 (2.30), 3.40 (2.70) vs 7.90 (1.70) in ascite volumes, respectively]. The apoptotic indexes of pancreas head and pancreas tail were all higher in treatment group than in model group at 6 h [P < 0.01, 0.00 (2.00)% vs 0.00 (0.00)%, 0.20 (1.80) vs 0.00 (0.00) in apoptosis indexes, respectively].

CONCLUSION: The mechanism of dexamethasone treatment in acute pancreatitis is related to its inhibition of inflammatory mediator generation and induction of pancreatic acinar cell apoptosis.

Keywords: Severe acute pancreatitis; Apoptosis; Inflammatory mediators; Dexamethasone; Tissue microarrays