Therapeutic Effect Of Trimetazidine On Severe Acute Pancreatitis With Acute Lung Injury In Rats

Objective: The establishment of severe acute pancreatitis with acute lung injury rat model,to observe the therapeutic effect of trimetazidine on severe acute pancreatitis with acute lung injury in rats and explore the mechanism trimetazidine in treatment of acute pancreatitis with acute lung injury.Methods:1 Clean grade of 72 healthy adult male SD rats(weight 220g-260g),were randomly divided into three groups: a control group,a study group,a trimetazidine treatment group.The study group and trimetazidine treatment group rats were induced with 5% sodium taurocholate(1ml/kg),the control group rats were done laparotomy,fliped the duodenum and touched pancreas gently,the trimetazidine treatment group rats were treated with trimetazidine(20mg/kg,dissolved in 10 ml saline)by gavage after modeling 1h,the control group and study group rats were given the same amount of saline.The rats in each group were followed for 3h,6h and 12 h after modeling.2 The pancreas tissue and lung tissue were observed under light microscope.3 Colorimetric method was used to detect the level of serum amylase and the level of MDA in lung tissue.4 Enzyme linked immunosorbent assay(ELISA)was used to detect the levels of serum TNF-α and IL-6.5 Immunohistochemical method was used to detect the expression of NF-κB in lung tissue.6 Western blot method to determine the protein expression of MPO and ICAM-1 in lung tissue.Results:1 With the extension of modeling,the rat pancreatic tissue showeddifferent degrees of edema,inflammatory infiltration,spotty or patchy hemorrhage,necrosis of the tissues around the pancreas,and ascites volume along with gradually increased at different time points.At the same time,there were different degrees of inflammatory infiltration in the lung tissue of rats,and there were different degrees of edema,hemorrhage,atelectasis and so on.Compared with the study group,the degree of pathological damage of pancreas and lung tissue were reduced,in the treatment group at the same time point,and the pathological score was statistically significant(P < 0.05).2 The serum amylase content increased along with modeling in study group,at the same sampling time points,serum amylase content of treatment group rats were lower than the dtudy group,but both were higher than the control group,the difference was statistically significant(P < 0.05).The level of MDA in lung tissue of study group was gradually increased with the time of modeling,the rats in treatment group were lower than the study group at the same time point,the difference was statistically significant(P < 0.05).3 The levels of serum TNF-αwas higher than the control group of the study group and treatment group at the same time point,two groups reached the peak after modeling 3h,then decreased slowly,the treatment group is lower than the study group at each time point,the difference was statistically significant(P < 0.05).The levels of serum IL-6 was higher than the control group of the study group and treatment group at the same time point,two groups reached the peak at 6h,12 h was slightly decreased,the treatment group was decreased than the study group at each time point,the differences were statistically significant.(P < 0.05).4 The expression of NF-κB in lung tissue of study group and treatment group was higher than that of the control group at each time point.The expression of NF-κB reached the peak at 6h,and the 12 h decreased slightly,but remained at a high level.The expression of NF-κB in treatment group was lower than that in study group at each time point,the difference was statistically significant(P < 0.05).5 The expression levels of ICAM-1 and MPO in lung tissue of studygroup and treatment group were higher than control group at each time point.The expression of ICAM-1 in the lung tissue of study group increased gradually with the modeling time.The expression of MPO in lung tissue peaked at 6h after modeling,and 12 h decreased slightly.The expression of ICAM-1 and MPO in the lung tissue of the treatment group was lower than the control group at the same time point,the difference was statistically significant(P < 0.05).Conclusion:1 Trimetazidine had the effects of anti-inflammatory and reducing ischemia,could inhibit the releasing of inflammatory factor(TNF-α,IL-6)significantly,and inhibited the activation of NF-κB signaling pathway,cut the expression of lung tissue ICAM-1.At the same time,it could scavenge the oxygen free radical that had exist,so as to reduce the damage of pancreas and lung tissue.Trimetazidine is a therapeutic effect of acute pancreatitis with pulmonary injury.