Experimental Study On Acute Lung Injury In Rats With Severe Acute Pancreatitis

1. The induction of the model of the severe acute pancreatitis associatedwith acute lung injuryObjective To induce the model of the acute lung injury(ALI) in severe acute pancreatitis (SAP) in rats. Methods Thirty SD rats were randomly divided into five groups: sham operation group(SO group) and SAP group 1,4,8,12 hour.SAP model was established by retrograde injection of 5% sodium taurocholate into biliopancreatic duct.The ascitic fluid and serum amylase were detected,the blood gas analysis were performed.The pathology of pancreas and lungs was recorded and compared between the groups. Results The ascitic fluid and serum amylase were gradually increased.The blood pressure of O₂ was decreased,while that of CO₂ was heightened. Histologically, massive alveolar edema, hemorrhage, and inflammatory cell infiltration were observed in lungs. Conclusions The model of ALI in SAP can be established by retrograde injection of 5% sodium taurocholate into biliopancreatic duct.2. Experimental Study on the pathogenesis of the acute lung injury inrats with severe acute pancreatitisObjective To study the pathogenesis of the ALI in rats with SAP. Methods Thirty SD rats were randomly divided into five groups: SO group; SAP group 1,4,8,12 hour.SAP model was established by retrograde injection of 5% sodium taurocholate into biliopancreatic duct. The lung homogenates were prepared to detect Nuclear factor- κB (NF- κB) activity by EMSA,the expression ICAM-1 by Western blot. Serum cytokine(TNF- a and IL-lp) were measured by ELISA and the expressions of TNF- a mRNA and IL-ipmRNA were observed by RT-PCR. The pulmonary pathology was recorded to assess lung injury and compared between the groups. Results In SAP group, NF- k B activity in lung homogenates increased markedly, while there was no marked expression of NF- k B in SO group (PO.01). NF- k B activity in lung homogenates increased markedly from (5168.5±728.4) at 1 hour to (12243.2±1252.3) at 12 hour. Serum TNF- a and IL-ip level increased significantly in ALI rats as compared with that in SO group.The level of serum TNF- a increased significantly at 1 hour(150.3±20.7 pg/ml), compared with SO group(55.3±6.5 pg/ml).While the level of serum IL-1J3 increased obviously at 4 hour (182.7±30.6 pg/ml),compared with SO group (85.8±25.5 pg/ml). Compared with SO group,TNF-a mRNA,IL-l(3mRNA, myeloperoxidase (MPO) and ICAM-1 expression in lung homogenates increased obviously after sodium taurocholate injection.Histologically,massive alveolar edema, hemorrhage,and inflammatory cell infiltration were observed. NF- k B was correlated with TNF-amRNA and the severity of ALI(r=0.94,0.87, PO.01). The expressions of TNF-amRNA and ICAM-1 were correlated with the severity of ALI(r=0.85,0.88,P<0.01). The expression of ICAM-1 was also correlated with MPO(r=0.91,P<0.01). Conclusions The increase of TNF- a and IL-lp in blood,the over-expression of TNF- a mRNA and IL-l(3mRNA and ICAM-1 in lung tissue may play an important role in the development of SAP. NF- k B is involved in the inflammation response of rat SAP and is specifically related with lung injury.The mechanism might be associated with the activation of NF-kB activation and then the increased expression of TNF-a,IL-lj3 and ICAM-1.3. Treatment of acute lung injury in severe acute pancreatitis with largedosage of dexamethasone in ratsObjectives To observe the therapeutic effects of large dosage of dexamethasone(DXM) on ALI in rats with SAP. Methods Thirty six SD rats were randomly divided into two groups: SAP group and Group of SAP treated with DXM(DXMgroup).The NF- k B expression of lung was detected by EMSA, whereas the serum levels of TNF- a and IL-lp were estimated by ELISA. TNF- a mRNA and MPO in pulmonary homogenate were determined at 4,8 and 12 hour after SAP induced. Meanwhile,the pathological changes of lungs were examined and compared between the groups. Results Compared with SAP group,in DXM group serum TNF-a and IL-1J3 level significantly reduced at 4,8 and 12 hour.In DXM group,the pulmonary TNF-a mRNA content were decreased.In DXM group,pulmonary MPO activity were also decreased at 4,8 and 12 hour,and pulmonary pathologic severity significantly ameliorated. In the SAP group,NF- k B in pulmonary tissue were over-expressed,while in DXM group,the expression of NF- k B were significantly lower than those in SAP group(P<0.01).The lung pathological changes were also obviously alleviated in DXM group as compared with SAP group(P<0.01). Conclusions NF- k B is involved in the inflammation response of ALI with SAP in rat and is specifically related with lung injury.Therapeutic DXM is effective in improving acute lung injury in SAP,probably through the inhibition of the expression of NF- k B,SIRS and the activation of leukocytes.