Effects of Kupffer cells on coagulation function of rats with acute pancreatitis through tissue factor

Abstract:

Objective：To observe the changes of tissue factor（TF） and coagulation function in rats with acute pancreatitis（AP） and to explore the role of Kupffer cells（KCs） in cruor function in AP rats via TF. Methods：Totally 108 SD rats are randomly divided into 6 groups including sham operation（SO） group，mild acute pancreatitis（MAP） group，severe acute pancreatitis（SAP） group，SO+gadolinium chloride（Gdcl3） group，MAP+Gdcl3 group，SAP+Gdcl3 group. Rats in Gdcl3 pretreatment group were injected with Gdcl3（10 mg/kg，0.1 ml） through the vena caudalis at 24 h before the establishment of AP model. Rats were retrograde infected with 1.5% or 5% of sodium taurocholate through bile duct to establish MAP model and SAP model. The rats were killed at 6，12，24 h after AP treatment or sham operation. Changes in serum amylase and coagulation makers were detected. The content of TF in serum was measured by ELISA. KCs was isolated and cultured， and then the expression of TF protein was detected by Western blot. The TF expression in liver tissues was measured by immunohistochemistry. The pathological damage of the pancreatic tissue was detected by HE staining. Results：The content of serum amylase was significantly higher in MAP and SAP group than in SO group（P<0.01），while there was no significant difference between MAP group，SAP group and MAP+Gdcl3 group，SAP+Gdcl3 group. The contents of TF markedly increased in MAP and SAP groups compared with those in SO group， while distinctively decreased compared with those in MAP+Gdcl3 and SAP+Gdcl3 group（P<0.05）. The TF protein expressions in the livers of rats in MAP and SAP groups distinctively increased compared with those in SO group. TF protein contents of KCs were obviously lower in MAP+Gdcl3 and SAP+Gdcl3 groups than in MAP and SAP groups（P<0.05）. Plasma concentrations of the prothrombin time（PT），activated partial thrombo-plastin time（APTT） and fibrinogen（FIB） in SAP group obviously increased compared with those in MAP groups and SO groups while markedly decreased in SAP+Gdcl3 group compared with those in SAP group（P<0.05）. The pathological section of rat pancreas showed that the pancreatic interstitial of MAP group was oedematous while the pathological damage of MAP+Gdcl3 group was alleviatived compared with that of MAP group. Pancreas of SAP group was in coagulation necrosis with a large number of inflammatory cells while the pathological damage of SAP+Gdcl3 group was obviously alleviatived compared with that of SAP group. Conclusion：Significant increases of TF expression of KCs leading to the change of coagulation makers after the onset of AP. TF expression and the coagulation can be effectively reduced by inhibiting KCs，which can reduce the occurrence and development of AP to some extent.