| The incidence of acute pancreatitis showed an increasing trend, and the multiple-organ dysfunction syndrome is one of the most intractable problems in the treatment of severe acute pancreatitis. Sivelestat sodium is a novel neutrophil elastase inhibitor, and some studies have shown its therapeutic effects on variety of organ injuries that reacted from inflammatory. Aim of the research is to evaluate the therapy effects of sivelestat against severe acute pancreatitis (SAP) in rats and investigate its potential mechanism. The SAP models were induced by retrograde injection of4%sodium taurocholate into bilopancreatic duct of SD rats, and the P group rats are therapies with Sivelestat0.2mg/kg/hr from caudal vein injection after model were induced. Histopathology of pancreas, lung, kidney and liver were observed dynamically, and NE, TNF-a, IL-6, Amy, BUN were detected; Activities of NE, MDA and SOD in liver tissue were measured, apoptosis of hepatocytes were detected and apoptosis index (AI) were calculated, the expression of Bcl-2and Bax were determined. We found that treatment with sivelestat can reduce the serum contents of NE、TNF-a and IL-6, and release the pathological damages of the pancreas, lung, kidney, liver tissue, and serum enzymologist indicators. The contents of NE and MDA in liver tissue were reduced; SOD level and the ratio of Bcl-2/Bax gene expression were improved, thus the apoptosis of hepatocytes were alleviated. So we can draw these conclusions:Sivelestat has a protective effect on the multiple organ injury in severe acute pancreatitis, and it can reduce the NE and MDA content of the liver tissue, enhance SOD and Bcl-2/Bax gene expression levels thus reduced the hepatocyte apoptosis.Part1Protective effects and mechanisms of sivelestat against multiple-organ injuries induced by severe acute pancreatitis in rats[Abstract] Objective To evaluate the protective effects of sivelestat against multiple-organ injuries induced by severe acute pancreatitis (SAP) in rats and investigate its potential mechanism. Methods Eighty-four male Sprague-Dawley rats were average divided into three groups randomly:group C (Control group), group P (SAP group) and group S (SAP+sivelestat group). The SAP models were induced by retrograde injection of4%sodium taurocholate into bilopancreatic duct of SD rats. Group C rats were injected by isometric physiological saline. P group rats were treated with Sivelestat0.2mg/kg/hr through caudal vein injection after models were induced. Serum levels of TNF-α、IL-6、NE、Amy、ALT、AST、BUN、Cr、PaO2and dry/wet ratio of lung were measured at3,6, and12h after operation. Histopathology changes of pancreas, lung, kidney and liver were observed. Results In group P, Serum levels of TNF-α、IL-6、NE、Amy、ALT、AST、BUN、Cr、PaO2and dry/wet ratio of lung were significantly decreased after operation as compared with group P (P<0.01). Histopathology showed that the injuries of pancreas, lung, kidney and liver in group P were gradually aggravated with disease progression, and alleviated obviously with sivelestat treatment. Conclusions Sivelestat can inhibit the release of NE、TNF-a and IL-1, thus resist multiple-organ injuries induced by severe acute pancreatitis in rats.Part2The effects of sivelestat on hepatocyte apoptosis and Bcl-2/Bax expression after severe acute pancreatitis of rats[Abstract] Objective To investigate the effects of sivelestat on hepatocyte apoptosis and Bcl-2/Bax expression of severe acute pancreatitis(SAP) rats, and investigate its potential mechanism. Methods Fifty-four male Sprague-Dawley rats were average divided into three groups randomly:group C (Control group), group P (SAP group) and group S (SAP+sivelestat group). The SAP models were induced by retrograde injection of4%sodium taurocholate into bilopancreatic duct of SD rats. Group C rats were injected by isometric physiological saline. P group rats were therapies with Sivelestat0.2mg/kg/hr caudal vein injection after model were induced. Activations of neutrophil elastase (NE), malondialdehyde (MDA) and superoxide dismutase (SOD) in liver tissue were measured3,6, and12h after operation. Hepatocytes apoptosis were detected with terminal deoxynuceotidy transferase mediated dUTP nick end labeling (TUNNEL) and apoptosis index (AI) were calculated, hepatocellular apopotosis rates were detected with flow cytometer. The expression of Bcl-2and Bax were determined by Western blot. Results Compared with group C, apoptosis index and apopotosis rates of hepatocytes were increased in group P; the NE and MDA activities of liver were increased and the SOD activities were depressed; the expression of Bcl-2were decreased and the expression of Bax were increased. Compared with group P, the serum levels of NE, apoptosis index and apopotosis rates of hepatocytes, the MDA activities and the expression of Bcl-2of group S were depressed; but the SOD activities and the expression of Bcl-2were heightened. Conclusions Sivelestat can depress the hepatocyte apoptosis of SAP rats. The mechanisms maybe related to the inhibition of neutrophile elastase and oxygen radicals, thus up-regulating the ratio of Bcl-2/Bax. |
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