Protective mechanism of rosiglitazone on acute necrotizing pancreatitis associated lung injury in rats

Objective To investigate the protective effect of rosiglitazone on acute necrotizing pancreatitis (ANP) associated lung injury in rats.Methods Seventy-five male Wistar rats were randomly divided into sham operation group (SO group),acute necrotizing pancreatitis group (ANP group) and rosiglitazone pretreatment group (ROSI group).ANP model was induced by retrograde infusion of 5％ sodium taurocholate into the biliopancreatic duct.Thirty minutes after ANP induction,ANP groups were injected with 10％ DMSO (0.2 ml/100 g) through femoral vein,and ROSI group were injected with ROSI dissolved with 10％ DMSO (6 mg/kg) through femoral vein,while SO group was injected with normal saline,and 30 minutes later was injected with same amount of 10％ DMSO.Rats were sacrificed at 3 h,6 h and 12 h after the operation.Serum amylase and lung wet/dry weight ratio (W/D) were measured,lung tissues were harvested for pathologic examinations.STAT1 protein and phosphorylation-STAT1 protein (p-STAT1) expression were detected by Western blot.Results The serum levels of amylase,lung W/D,pathologic score of lung tissues in ANP group were increased with time,and reached the peak at 12 h,which were (5017 ± 203)U/L,3.12 ±1.30,(3.33 ±0.18) score,and these were significantly higher than those in SO group (P ＜ 0.05 or 0.01),the expression of STAT1 protein was not statistically significant,but the expression of p-STAT1 reached the peak at 3 h (5.23 ± 0.03),then it gradually decreased,but it was still significantly higher than that in SO group (0.16 ± 0.04,p ＜ 0.01).The serum levels of amylase,lung W/D,pathologic score of lung tissues in ROSI group at 12 h were (1912 ± 164) U/L,1.83 ± 1.26,(2.78 ± 0.16),which were significantly lower than those in ANP group (P ＜ 0.05).The expression of STAT1 protein was not statistically significant,and the expressions of p-STAT1 at 3 h,6 h,12 h was 0.41 ±0.04,0.22±0.05,0.15 ±0.03,which were significantly lower than those in ANP group (P ＜ 0.05).Conclusions Rosiglitazone has the protective effect on ANP associated lung injury by inhibition of phosphorylation-STAT1 protein expression in the early phase. Key words: Pancreatitis, acute necrotizing;  Peroxisome proliferator-activated receptors; Rosiglitazone;  Lung injury