ABSTRACT
Severe acute pancreatitis (SAP) is normally related to multiorgan dysfunction and local complications. Studies have found that local pancreatic renin-angiotensin system (RAS) was significantly upregulated in drug-induced SAP. The present study aimed to investigate the effects of angiotensin II receptors inhibitor valsartan on dual role of RAS in SAP in a rat model and to elucidate the underlying mechanisms. 3.8% sodium taurocholate (1 ml/kg) was injected to the pancreatic capsule in order for pancreatitis induction. Rats in the sham group were injected with normal saline in identical locations. We also investigated the regulation of experimentally induced SAP on local RAS expression in the pancreas through determination of the activities of serum amylase, lipase and myeloperoxidase, histological and biochemical analysis, radioimmunoassay, fluorescence quantitative PCR and Western blot analysis. The results indicated that valsartan could effectively suppress the local RAS to protect against experimental acute pancreatitis through inhibition of microcirculation disturbances and inflammation. The results suggest that pancreatic RAS plays a critical role in the regulation of pancreatic functions and demonstrates application potential as AT1 receptor antagonists. Moreover, other RAS inhibitors could be a new therapeutic target in acute pancreatitis.
Subject(s)
Animals , Rats , Amylases , Blotting, Western , Fluorescence , Inflammation , Intercellular Adhesion Molecule-1 , Lipase , Microcirculation , Models, Animal , P-Selectin , Pancreas , Pancreatitis , Peroxidase , Polymerase Chain Reaction , Radioimmunoassay , Receptors, Angiotensin , Renin-Angiotensin System , Taurocholic Acid , ValsartanABSTRACT
Objective To investigate the effect of administration intravenously of rosiglitazone (ROSI) on severe acute pancreatitis (SAP) in rats and its mechanisms. Method Fifty-four male Wistar rats were randomly divided into sham operation group (SO group), severe acute panereatitis model group (SAP group) and rosiglita-zone pretreatment group (ROSI group),18 rats in each group.SAP model was induced by retrograde inufsion of 5% sodium taurecholate into the biliopancreatic duct. The rats in SO group and SAP group were injected with 10% DMSO (0.2 ml/100 g) by femoral vein 30 minutes piror to the operation. In ROSI group,rosiglitazone partes ae-quales(6 mg/kg) was injected instead of 10% DMSO. Rats were killed at 3, 6 and 12 h after operation. Serum amylase level and myelopemxidase activity were detected. Pancreatic tissue samples were stained with hematoxylin and eosin for histopathological evaluation. Reverse transcription-polymerase chain reaction was used for detecting the levels ofTNF-α mRNA and ICAM-1 mRNA in pancreatic tissue. Results Amylase level, myeloperexidase ac-tivity, pathologic score and the expression of TNF-α and ICAM-1 mRNA were increased significantly in SAP group at each time point than those in SO group (P<0.05). Compared with SAP group, pretreatment with rosiglitazone reduced serum amylase level and pathologic score at time point of 6 h and 12 h (P<0.05), decreased myeloper-oxidase activity at 12 h (P<0.05), downregulatied the expression of TNF-α mRNA at all time pointy, (P<0.05),ICAM-1 mRNA at 6 h and 12h(P<0.05). Conclusions Rosightazone has the effect on pancreatitis in SAP through downregulating the expression of TNF-α mRNA and ICAM-1 mRNA.