Effects of Peroxisome Proliferator-Activated Receptor-γ Activation on Apoptosis in Rats with Acute Pancreatitis
- 426 Downloads
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.
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.
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.
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.
KeywordsSAP rat MAP rat Pioglitazone Apoptosis PPAR-γ
This work was supported by grants from the Scientific Foundation of Shanghai Scientific and Technologic Bureau (10ZR1427900) and Medical leading cooperative project supported by Songjiang district health bureau of Shanghai City (2011LX01).
Conflict of interest
- 18.Sikka S, Chen L, Sethi G, et al. Targeting PPARγ signaling cascade for the prevention and treatment of prostate cancer. PPAR Res. 2012;2012:968040. doi: 10.1155/2012/968040.
- 19.Ogawa Y, Yoneda M, Tomeno W, et al. Peroxisome proliferator-activated receptor gamma exacerbates concanavalin A-induced liver injury via suppressing the translocation of NF-κB into the nucleus. PPAR Res. 2012;2012:940384. doi: 10.1155/2012/940384.