| ObjectiveTo investigate the effect and mechanism of sivelestat sodium in acute lung injurysecondary to Severe acute pancreatitis(SAP)in rats by observing the levels of NE andICAM-1in serum,the expression of NF-κB and caspase-3in lung tissue,pathological changes of the pancreas and lung tissue.MethodsFifty-four adult SD rats were randomly(random number)divided into controlgroup(C group，n=18)，ALI group(A group，n=18)and sivelestat sodium treatmentgroup(S group， n=18).Each group was randomly divided into threegroups(3h,6h,12h,n=6cases).The model of SAPALI was eastablished by injecting1ml/kg of sodium tauarocholate into the pancreatic capsule of the rats in A group and Sgroup.The model rats in S group were treated with sivelestat sodium via right jugularvein catheterizationone10minutes after modelin.Six rats of each group weresacrificed on the three time points:the third hour,the fifth hour,the seventh hour(six inevery group),observe pathological change and score,collect blood serum to textamylase(AMS),the levels of NE and ICAM-1in plasma were assessed by enzymelinked immunosorbent assay(ELISA),and then the expression of NF-κB and caspase-3in lung was detected by Immunohistochemistry,the level of apoptosis were assessedby TUNNEL.Results1:The pathological score of lung (osman lung histology scoring criteria):Thehistopathology score of group A was significantly higher than it is in group C all thetime(P<0.01),and The pathological score is a Increasing trend according to thetime(P<0.01).Compared with group A,The histopathology score is significantly lowerin group S at3h,6h(P<0.01) and the difference was statistically significant at12h(P<0.05). 2:The level of amylase in serum is much higher in group A than it is in group C ateach time point(P<0.01),the data is a increasing trend according to thetime(P<0.01).Compared with group S,the level of amylase in serum is significantlydecreased compared with group A at6h,12h after intervention(P<0.01),but there is nostatistical difference at3h(P>0.05).3:Compared with group C, the levels of NE were significantly increased in group Aat6h,12h(P<0.01) and the difference was statistically significant at3h(P<0.05),thelevel of NE in group A is a Increasing trend according to the time(P<0.01).The levelof NE in group S is significantly lower than group A at6h and12h(P<0．05),but nosignificant differance at3h(P>0.05).4:The expression of ICAM-1of group A was significantly higher than it is in groupC all the time(P<0.01),and this data is a increasing trend according to thetime(P<0.01).Compared with group A,the histopathology score is lower in group S allthe time,the difference was statistically significant at3h(P<0.05) and this datadecreased significantly at6h,12h(P<0.01).5:The expression of NF-κB in the pulmonary tissue were increased significantly ingroup A than it is in group C(P<0.01),in group A,this data is the highest on time point6h.Compared with group S,the expression of NF-κB is significantly decreasedcompared with group A at6h after intervention(P<0.01),the difference wasstatistically significantat12h(P<0.05),but there is no statistical difference at3h(P>0.05).6:The level of caspase-3increased significantly in group A than group C at eachtime point(P<0.01),and compared with group A, the levels of caspase-3weresignificantly decreased in the group S alla the time(P<0.01).7:The apoptosis rate was lower in group C than group A and S(P<0.01),comparedwith group A,this rate was higher than group S at each time point (P<0.01).8:The level of NE in serum was correlated closely and positively with Thepathological score of lung,the expression of caspase-3in lung tissue,the level ofICAM-1in serum;and the expression of caspase-3was correlated closely and the levelof ICAM-1in serum. Conclusion1.The signal of NF-κB was rapidly activated after operation in early stage of acutepancreatitis-associated lung injury(APALI), as well as ICAM-1and NE inserum,significant inflammatory reaction and severe lung injury were confirmed,whichwere well associated with the progress and aggravation of APALI.2.Sivelestat sodium can inhibit NF-κB activation and control inflammation, reducecaspase-3expression and the apoptosis rate in lung tissue, decrease the levels of NEand ICAM-1in serum, has a therapeutic effect on SAPALI. |
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