title: Effects of peroxisome proliferator-activated receptor-γ activation on apoptosis in rats with acute pancreatitis.
abstract: OBJECTIVE
  To investigate the effects and mechanisms of peroxisome proliferator-activated receptor-γ (PPAR-γ) 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-γ. The expression of inflammatory factors (TNF-α 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-γ proteins were elevated in the pancreases of SAP or MAP rats pre-injected with pioglitazone intraperitoneally. Downregulation of the expression TNF-α 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-κB.
  
  
  CONCLUSIONS
  These results indicated that activation of PPAR-γ induced apoptosis in pancreatic acinar cells of SAP rats but inhibited apoptosis in pancraeatic acinar cells of MAP rats, which demonstrated that PPAR-γ may be an efficiently therapeutic target in pancreatic inflammation.
authors.affiliation: Department of Gastroenterology, Songjiang Hospital Affiliated First People's Hospital, Shanghai Jiao Tong University, Shanghai, 201600, China, sjzxxp@yeah.net.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Lou
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.forename: Zhi-Wen
authors.initials: ZW
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism* / Q000502:physiology; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D000077205:Pioglitazone; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D051996:Transcription Factor RelA / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D051996:Transcription Factor RelA; C505410:Casp3 protein, rat; D053148:Caspase 3; D000077205:Pioglitazone