Induction of apoptosis by artemisinin relieving the severity of inflammation in caerulein-induced acute pancreatitis.
OBJECTIVE
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-kappaB) activation was detected by flow cytometry. Macrophage inflammatory protein-1alpha (MIP-1alpha) protein was measured by Western blot. Interleukin-1beta (IL-1beta) 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-kB (29% +/- 4.1% vs 42% +/- 5.8%), MIP-1alpha 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-1beta mRNA (1.7 +/- 0.3 vs 2.4 +/- 0.4) in the apoptosis inducing group was obviously decreased (P < 0.05).


CONCLUSIONS
Inducing apoptosis can relieve pathological impairment and inflammatory reaction in AP rats.
Zhao
Ming
M
Department of General Surgery, First Clinical College, Harbin Medical University, Harbin 150001, Heilongjiang Province, China.
Xue
Dong-Bo
DB
Zheng
Biao
B
Zhang
Wei-Hui
WH
Pan
Shang-Ha
SH
Sun
Bei
B
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D037621:Artemisinins / Q000494:pharmacology* / Q000627:therapeutic use; D053148:Caspase 3 / Q000378:metabolism; D002108:Ceruletide / Q000633:toxicity; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D037621:Artemisinins; D016328:NF-kappa B; D002108:Ceruletide; C031327:artemisinin; D009195:Peroxidase; D053148:Caspase 3