Effect of specific thromboxane synthase inhibitor on pancreas and lung injury in dogs with acute necrotizing pancreatitis

Abstract

Objective To study the role of specific thromboxane synthase inhibitor in dogs with acute necrotizing pancreatitis (ANP) associated lung injury and investigate the possible mechanism.Methods Twenty healthy male mongrel dogs were randomly divided into simple operation group (control group,n =4),ANP model group (ANP group,n =8) and ANP model with specific thromboxane synthase inhibitor (Ozagrel) treatment group (treatment group,n =8).The ANP model was induced by retrograde injection with 5％sodium taurocholate and trypsin into the pancreatic duct.The treatment group was given intravenous infusion of Ozagrel (2 mg/kg,twice a day for 7 days) 2 h after the induction of ANP model.The serum calcium,hypersensitive C-reactive protein (HCRP),thromboxane A2(TXA2),prostacyclin (PGI2) levels were monitored dynamically.Seven days later,the dogs were sacrificed,pancreas and lung tissues were harvested for pathological examinations and scored.Results No obvious pathological changes were seen in pancreas and lung tissues in control group,but significant pathological changes were observed in ANP group,and the pathological changes in treatment group were attenuated.The pathological scores of pancreas in control group,ANP group and treatment group were (1.25 ± 0.96),(7.00 ± 2.39),(4.63 ± 1.19),and the pathological scores of lung were (0.75 ± 0.50),(7.13 ± 1.55),(4.88 ± 0.83),and the values in ANP group and treatment group were significantly higher than that in control group,in addition,the value in treatment group was significantly lower than that in ANP group (P ＜ 0.05).The serum levels of calcium,HCRP,TXB2,keto PGFla and TXB2/keto PGFla ratio were (2.45 ± 0.07) mmol/L,(30.36 ± 4.29) mg/L,(345.8 ± 46.8) pg/ml,(187.8 ± 18.6)pg/ml,1.85 ± 0.16 in control group 1 d later; the corresponding values in ANP group were (2.21 ± 0.08) mmol/L,(72.04 ± 10.22) mg/L,(1227.3 ± 118.2) pg/ml,(368.8 ± 64.4) pg/ml,3.33 ± 0.19; and the corresponding values in treatment group were (2.32 ± 0.08) mmol/L,(66.51 ± 4.28)mg/L,(1179.5 ± 116.3) pg/ml,(371.8 ± 65.2) pg/ml,3.17 ± 0.18.The serum levels of calcium in ANP group and treatment group were significantly lower than that in control group,but other parameters were significantly increased,and the difference among the 3 groups was statistically significant (P ＜ 0.01).The serum level of calcium in treatment group was significantly higher than that in ANP group,while the serum level of HCRP was significantly lower than that in ANP group,and the difference between the two groups was statistically significant (P ＜ 0.01).Conclusions The pancreas and lung injury in dogs with acute necrotizing pancreatitis is attenuated with specific thromboxane synthase inhibitor treatment,and its mechanism may be blockade of TXA2 synthesis,correction of TXA2/PGI2 imbalance and improved pancreas and lung microcirculation. Key words: Pancreatitis, acute necrotizing; Lung injury; Thromboxane A2 ; Prostacyclin