Pioglitazone inhibits P38MAPK expression in rats with acute necrotizing pancreatitis

Objective Peroxisome proliferators-activated receptor γ(PPARγ) plays a protective role against acute necrotizing pancreatitis(ANP),but its mechanism remains unclear.This study is to investigate the effects of pioglitazone on the expression of P38 mitogen-activated protein kinase(P38MAPK) and related cytokines in rats with ANP,and to explore its therapeutic mechanism.Methods Fifty-four male Wistar rats were randomly divided into a sham-operation group,an ANP group and a pioglitazone group.ANP was induced by retrograde injection of 4% sodium taurocholate(0.1 ml/100 g) into the biliary and pancreatic duct.The sham-operation group was injected with normal saline,while the pioglitazone group with pioglitazone at 20 mg/kg before ANP induction.All the rats were sacrificed 3,6 and 12 h after ANP induction for the measurement of the levels of serum amylase,TNF-α and IL-1β,and pancreatic tissues were harvested for pathological examination by light microscopy and determination of the P38MAPK expression by Western blotting.Results The concentrations of serum amylase,levels of TNF-α and IL-1β,scores on pancreatic histology were significantly higher at all time points in the ANP group than in the sham-operation group(P0.01).Compared with the ANP group,the levels of serum amylase,TNF-α and IL-1β were significantly reduced(P0.05) and the pancreatic injury obviously milder in the pioglitazone group.The expression of P38MAPK in the pancreatic tissue was slight in the sham-operation group,but significantly elevated in the ANP group,reaching the peak at 3 h after ANP induction(P0.01),and then gradually decreased.At all time points,the expression of P38MAPK was significantly lower in the pioglitazone group than in the sham-operation group(P0.05).Conclusion Pioglitazone could reduce the levels of serum TNF-a and IL-1β and lessen ANP-induced pancreatic lesions by inhibiting the activity of P38MAPK.