Lei Li1, Zhongwei Sun2, Caiming Xu2, Jun Wu3, Geliang Liu4, Hongzhang Cui5, Hailong Chen6. 1. Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, People's Republic of China; Department of Vascular Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, People's Republic of China. 2. Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, People's Republic of China. 3. Department of Ultrasound, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, People's Republic of China. 4. Department of Urology Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, People's Republic of China. 5. Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, People's Republic of China. 6. Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, People's Republic of China. Electronic address: hailongchen2017@163.com.
Abstract
AIMS: Severe acute pancreatitis (SAP) is a serious disease associated with systematic inflammation and multiple organs dysfunction. Soluble ST2 (sST2), a member of the Toll interleukin (IL)-1 receptor (TIR) superfamily, has been demonstrated to exert immune-regulatory and anti-inflammatory properties in several inflammation-related diseases. In this study, we investigated whether transfer of sST2 gene by adenovirus vector could attenuate sodium taurocholate-induced SAP and associated cardiac injury. MAIN METHODS: A rat model of SAP was induced by retrograde injection of 5% sodium taurocholate (1 ml/kg) into the biliopancreatic duct. Rats in the treatment groups were intravenously injected with adenovirus expressing sST2 (Ad-sST2, 1 × 109 particles/rat) or green fluorescent protein (Ad-GFP) via the tail vein 48 h before SAP induction. Histological changes in the pancreatic and heart tissues, and parameters for evaluating SAP and associated cardiac injury were determined at 24 h after SAP. KEY FINDINGS: Sodium taurocholate induced obvious pathological changes in pancreas and elevated serum levels of amylase and lipase. Furthermore, SAP animals exhibited significant cardiac impairment, evidenced by decreased cardiac function, increased myocardial apoptosis and cardiac-related enzymes including creatine kinase isoenzyme, lactate dehydrogenase, and Troponin T. Administration of Ad-sST2 markedly improved the structure of pancreas and heart tissues, and reversed the alterations in serum amylase, lipase and cardiac-related enzymes. In addition, Ad-sST2 treatment downregulated pro-inflammatory cytokines production, demonstrating the anti-inflammatory property of sST2. SIGNIFICANCE: Our results suggest that administration of Ad-sST2 significantly attenuated the severity of SAP and associated cardiac damage, and the cardioprotective effect is associated with its anti-inflammatory action.
AIMS: Severe acute pancreatitis (SAP) is a serious disease associated with systematic inflammation and multiple organs dysfunction. Soluble ST2 (sST2), a member of the Toll interleukin (IL)-1 receptor (TIR) superfamily, has been demonstrated to exert immune-regulatory and anti-inflammatory properties in several inflammation-related diseases. In this study, we investigated whether transfer of sST2 gene by adenovirus vector could attenuate sodium taurocholate-induced SAP and associated cardiac injury. MAIN METHODS: A rat model of SAP was induced by retrograde injection of 5% sodium taurocholate (1 ml/kg) into the biliopancreatic duct. Rats in the treatment groups were intravenously injected with adenovirus expressing sST2 (Ad-sST2, 1 × 109 particles/rat) or green fluorescent protein (Ad-GFP) via the tail vein 48 h before SAP induction. Histological changes in the pancreatic and heart tissues, and parameters for evaluating SAP and associated cardiac injury were determined at 24 h after SAP. KEY FINDINGS:Sodium taurocholate induced obvious pathological changes in pancreas and elevated serum levels of amylase and lipase. Furthermore, SAP animals exhibited significant cardiac impairment, evidenced by decreased cardiac function, increased myocardial apoptosis and cardiac-related enzymes including creatine kinase isoenzyme, lactate dehydrogenase, and Troponin T. Administration of Ad-sST2 markedly improved the structure of pancreas and heart tissues, and reversed the alterations in serum amylase, lipase and cardiac-related enzymes. In addition, Ad-sST2 treatment downregulated pro-inflammatory cytokines production, demonstrating the anti-inflammatory property of sST2. SIGNIFICANCE: Our results suggest that administration of Ad-sST2 significantly attenuated the severity of SAP and associated cardiac damage, and the cardioprotective effect is associated with its anti-inflammatory action.