The Expression Of NF-κB, ICAM-1 And Caspase-3 In Severe Acute Pancreatitis-assosiated Lung Injury And The Effect Of Pioglitazone On These Factors

Objective:To study the role of NF-κB, ICAM-1 and caspase-3 in the pathogenesis of acute pancreatitis-associated lung injury in rats, and the effect of pioglitazone, a ligand of peroxisome proliferator-activated receptor gamma, on these factors.Methods:Fifty-four male Sprague-Dawley rats (160-200g) were randomly allocated into three groups: sham group(group C); SAP group(group A); treatment with pioglitazone group(group T). The model of SAP was induced by the retrograde injection of 5% sodium taurocholate in the pancreatic duct, 10%DMSO(10ml/kg) was injected intraperitoneally after operation. Sham-operated animals were executed operation, but nothing was injected, pancreas was just flipped and striked gently a few times. Pioglitazone (50mg/kg) was injected intraperitoneally after SAP immediately in group T. Rats were killed by abdominal aorta exsanguination at 3h, 6h and 12h after pancreatitis induced. Lung tissue was divided into two parts: one for histological examination and immunohistochemistry(IHC) was fixed in 10% formalin, anther for MPO determination was rapidly frozen in liquid nitrogen and then restored at -80℃. The activity of NF-κB, ICAM-1, Cleaved-Caspase 3 protein in lung tissue was examinated by IMH, and observed the effects of pioglitazone on them.Results:1. Lung histologic score: The scores were significantly elevated in group A compared with group C(P<0.01), which were decreased by pioglitazone at 12h (P<0.05).2. The activity of MPO in lung tissue: The levels of MPO in group A were significantly higher than group C at all time points. Compared with group A at 6h and 12h, those were reduced in group T(P<0.05).3. The lung expression of ICAM-1 protein: The positive stains mainly located in membrane or cytoplasm of vascular endothelial cells, bronchioles and alveolar epithelial cell in lung tissue which was weaker in sham group. The levels of ICAM-1 in group A and group T were significantly higher than group C at all time points(P <0.05). Compared with group A at12h, those were reduced in group T(P<0.05).4. The lung expression of NF-κBp65 protein: The activity of NF-κBp65 in group A was markedly upgraded compared with group C at all pionts (P<0.01), which was decreased significantly in group T compared with group A at 6h (P<0.05).5. The lung expression of Cleaved-Caspase 3: The activity of Cleaved-Caspase 3 in group A and group T was markedly upgraded compared with group C at all pionts (P<0.01), which was decreased significantly in group T compared with group A at 6h and 12h (P<0.05).Conclusions:The signal of NF-κB was rapidly activated after operation in early stage of acute pancreatitis-associated lung injury(APALI), as well as ICAM-1 and caspase-3 protein, which was well associated with the progress and aggravation of APALI; Pioglitazone played a protective role by inhibiting NF-κB activation, attenuating the lung expression of ICAM-1 and caspase-3 protein, which maybe a critical contributor to its antiinflammatory role.