Basic Research
Copyright ©2007 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 14, 2007; 13(42): 5612-5617
Published online Nov 14, 2007. doi: 10.3748/wjg.v13.i42.5612
Induction of apoptosis by artemisinin relieving the severity of inflammation in caerulein-induced acute pancreatitis
Ming Zhao, Dong-Bo Xue, Biao Zheng, Wei-Hui Zhang, Shang-Ha Pan, Bei Sun
Ming Zhao, Dong-Bo Xue, Biao Zheng, Wei-Hui Zhang, Bei Sun, Department of General Surgery, First Clinical College of Harbin Medical University, Harbin 150001, Heilongjiang Province, China
Shang-Ha Pan, The Key Laboratory of Hepatic-spleenic Surgery of Heilongjiang Province, Harbin 150001, Heilongjiang Province, China
Author contributions: All authors contributed equally to the work.
Supported by the Natural Science Foundation of Heilongjiang Province, China, No. D0227
Correspondence to: Wei-Hui Zhang, Department of General Surgery, First Clinical College, Harbin Medical University, Harbin 150001, Heilongjiang Province, China. zhangweihui626@hotmail.com
Telephone: +86-451-53658828 Fax: +86-451-53658828
Received: April 5, 2007
Revised: August 4, 2007
Accepted: August 31, 2007
Published online: November 14, 2007
Abstract

AIM: To observe the apoptosis and oncosis of pancreatic acinar cells and secondary inflammatory reaction in pancreatic tissue from rats with acute pancreatitis (AP), and the influences of artemisinin on them.

METHODS: AP was induced by 4 intraperitoneal injections of caerulein at 1 h intervals. To induce apoptosis, solution of artemisinin (50 mg/kg) was given intraperitoneally 1, 12, 24 and 36 h after the last caerulein injection. Histological examination of impairment of pancreatic tissue and detection of serum amylase were performed to evaluate the severity of acute pancreatitis. Apoptosis and oncosis were detected with acridine orange (AO) and ethylene dibromide (EB) staining. Caspase-3 and myeloperoxidase (MPO) activity were measured by colorimetric assay. Nuclear factor-kappa B (NF-κB) activation was detected by flow cytometry. Macrophage inflammatory protein-1α (MIP-1α) protein was measured by Western blot. Interleukin-1β (IL-1β) mRNA was detected by RT-PCR.

RESULTS: Addition of artemisinin increased the number of apoptotic cells (11.7% ± 1.4% vs 6.3% ± 0.7%, P < 0.05), while reduced the number of oncotic cells (13.0% ± 2.4% vs 17.5% ± 2.2%, P < 0.05). The activity of caspase-3 speeded up (1.52 ± 0.21 vs 1.03 ± 0.08, P < 0.05), the pancreas pathological impairment was relieved (3.0 ± 0.5 vs 4.0 ± 0.5, P < 0.05) and the level of serum amylase decreased (5642 ± 721 U/dL vs 7821 ± 653 U/dL, P < 0.05). The activation of NF-κB (29% ± 4.1% vs 42% ± 5.8%), MIP-1α protein (3.7 ± 0.5 vs 5.8 ± 0.7), MPO (0.52 ± 0.06 U/g vs 0.68 ± 0.09 U/g), IL-1β mRNA (1.7 ± 0.3 vs 2.4 ± 0.4) in the apoptosis inducing group was obviously decreased (P < 0.05).

CONCLUSION: Inducing apoptosis can relieve pathological impairment and inflammatory reaction in AP rats.

Keywords: Pancreatitis; Apoptosis; Inflammation mediators; Chemokines; Artemisinin