November 12, 2014
Notes: Xia, Qing
Sichuan Da Xue Xue Bao Yi Xue Ban. 2013 Nov;44(6):962-5.
Author Address: Department of integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Reference Type: Journal Article
Record Number: 4824Author: Xu, P., Lou, X. L., Chen, C. and Yang, Z. W.
Title: Effects of peroxisome proliferator-activated receptor-gamma activation on apoptosis in rats with acute pancreatitis
Journal: Dig Dis Sci
Short Title: Effects of peroxisome proliferator-activated receptor-gamma activation on apoptosis in rats with acute pancreatitis
Alternate Journal: Digestive diseases and sciences
ISSN: 1573-2568 (Electronic)
Accession Number: 24185678
Hypoglycemic Agents/pharmacology/therapeutic use
Pancreatitis/chemically induced/*drug therapy/*pathology
Severity of Illness Index
Transcription Factor RelA/metabolism
Abstract: PURPOSE: To investigate the effects and mechanisms of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activation on the induction of apoptosis in rats with acute pancreatitis. METHODS: Severe acute pancreatitis (SAP) and mild acute pancreatitis (MAP) were induced and pre-treated with pioglitazone, which is a ligand of PPAR-gamma. The expression of inflammatory factors (TNF-alpha and IL6) of the pancreas was detected by ELISA. The apoptosis in pancreas were detected by TUNEL assay and the activity of caspase 3 was determined. Phosphorylation of p65 in pancreas of SAP or MAP was determined by western-blot. RESULTS: Expression levels of PPAR-gamma proteins were elevated in the pancreases of SAP or MAP rats pre-injected with pioglitazone intraperitoneally. Downregulation of the expression TNF-alpha and IL6 and relief of pathological changes in the pancreas suggested that pioglitazone had protective effects on acute panceatitis. In pioglitazone pre-treated groups, a TUNEL assay indicated a high level of apoptosis in SAP but little apoptosis in MAP, showing pioglitazone could promote taurocholate-induced apoptosis but inhibit ceruleininduced apoptosis in pancraeatic aniniar cells. Furthermore, caspase 3 activity was high in SAP but low in MAP, implying that the apoptotic mechanism in pancreatic acinar cells of AP rats was correlated with caspase 3 activity. Phosphorylation of p65 was reduced in SAP or MAP group pretreated with pioglitazone, indicating that pioglitazone reduced the inflammation reaction by inhibiting the activation of the NF-kappaB. CONCLUSIONS: These results indicated that activation of PPAR-gamma induced apoptosis in pancreatic acinar cells of SAP rats but inhibited apoptosis in pancraeatic acinar cells of MAP rats, which demonstrated that PPAR-gamma may be an efficiently therapeutic target in pancreatic inflammation.