An Experimental Study On The Role Of Macrophage Migration Inhibitory Factor In Severe Acute Pancreatitis-Associated Lung Injury In Rats

Objective: To develop an severe acute pancreatitis-associated lung injury model in rats and evaluate the pathogenesis role of the cytokine,MIF,and AM in it.and so as to find more effective new therapeutic strategies.Methods: Rats were divided into three groups randomly. In the experimental group, severe acute pancreatitis-associated lung injury was induced in rats by retrograde injection 5% TCA(1 ml/kg body weight)into biliopancreatic ducts; In the control, Acute edema pancreatitis was induced in rats by retrograde injection 0.5% TCA(1 ml/kg body weight)into biliopancreatic ducts; In the intervention group, 0.2% GdCL+3(10mg/kg body weight) solution was injected in vena caudalis of rats. At 48h, 24 h before developing model. Then developed model by retrograde injection 5% TCA.The correlated indexes were evaluated at 1h, 3h, 6h, 9h, 12h after the model had been developed: MIFmRNA in the lung tissues was analyzed by semiquatitative reverse transcriptase polymerase chain reaction (RT-PCR). The expression of CD68 was evaluated by immunohistochemistry in rat lung tissues, Which represented the amount of macrophage; The levels of TNF-a were measured with enzyme linked immunosorbent assay(ELISA);The activity of MPO > tissue water content in lung and pulmonary histopathologic scoring were evaluated.Results:1 > Lung injury occurred at 3h after induction in the experimental group, the gradually aggratated. There were no the same manifestation in the control group.2> Pulmonary MIFmRNA levels increased obviously at lh after induction in the experimental group, then reached the climax at 3h.3 > There was the infiltration of macrophages in SAP associated lung injury at 3h after induction, and lasted along in large amount.4> The levels of TNF-ot and activity of MPO in the experimental groups increased obviously at 3h after induction, remained the high level until 12h.5> The expression of MIFmRNA showed strong positive correlation with the infiltrate number of macrophage, the level of TNF-ct in the experimental group.6> The number of macrophage showed positive correlation with the level of TNF-a and the activity of MPO.7n The administration of GdCL3 decreased the levels of pulmonary MIFmRNA and TNF-a in rats, the amout of macrophage,the activity of MPO and the lung water content decreased because of it also.Conclusions:1 -, Administrating 5%TCA by retrograde injected in bilipancreaticduct, Establishing rat SAP lung injury pattern , Lung injury occurred at 3h, injures increased gradually in the wake of time prolonged.2> In the pattern of the SAP lung injury, MIF which growed in number probably play significant actions, May inhibites macrophages removing, Moreover accelerates AM infiltrating locally and secreting such inflammation factors as TNF-a> IL-1 and so on .3? In SAP lung injures ,Assembleing of macrophage in the lung tissue is early than PMN infiltration .In ALI early phase ,macrophage probably play the role of "the trigger"in the response of PMN. AM is activated continuous and excessfully secrete massive mediators of inflammation,then AM further activat PMN. There are great deal of PMN in the alveolar space and pulmonary capillary, ultimately damage alveoli and permeability of capillary increase.4> Inhibiting the activity of macrophage can release the extent of lung injury.