Title: Effects of sivelestat on hepatocyte apoptosis and B lymphocytes/leukemia-2/bax expression in rats with severe acute pancreatitis
Abstract: Objective To investigate the effects of sivelestat on hepatocyte apoptosis and B lymphocytes/leukemia-2 (bcl-2)/bax expression of rats with severe acute pancreatitis (SAP),and the potential mechanism.Methods Fifty-four male Sprague-Dawley rats were equally 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 of 4% sodium taurocholate into bilopancreatic duct of SD rats.Group C rats were injected with isometric physiological saline.Group P rats were treated with sivelestat [0.2 tg/( kg· h)]via the caudal vein after models were induced.Serum levels of neutrophil elastase (NE),malondialdehyde (MDA) and superoxide dismutase (SOD) activity of liver tissue were measured 3,6,and 12 h after operation.Hepatocytes apoptosis was detected by using terminal deoxynuceotidy transferase mediated dUTP nick end labeling (TUNEL) and apoptosis index (AI) was calculated.Hepatocellular apopotosis rate was examined by using flow cytometer.The expression of bcl-2 and bax was detected by using Western blotting.Results As compared with group C,the serum levels of NE [ (5.62 ± 1.70),(6.83±2.01),(10.88±3.72) μg/L],hepatocytes AI (11.4±1.1,15.3 ±1.1,21.3 ±1.2) and apopotosis rate were increased at 3rd,6th,and 12th h after operation in the group P; the MDA activity of liver tissue [ (9.13 ± 1.32),( 1 1.62 ± 3.71 ),( 13.57 ± 3.29) nmol/mg ]was increased and the SOD activity [(154.00±22.38),(138.05 ±29.48),(122.63 ±28.71) U/mg]was reduced; the expression levels of bcl-2 were decreased and those of bax were increased.As compared with group P,the serum levels of NE [ (3.57 ±2.30),(4.11 ±2.16),(6.66 ±2.69) μg/L],hepatocytes AI (8.1 ±0.7,1 1.2 ±0.8,15.1 ±1.0) and apopotosis rate,the MDA activity [(5.75 ±0.86),(7.95 ±3.01),(9.77 ±3.45) nmol/mg]and the expression levels of bcl-2 in group S were depressed; but the SOD activity [ ( 187.12 ±37.39),( 179.23 ±44.59),( 163.55 ±25.79) U/mg]and the expression of bcl-2 were increased.Conclusion Sivelestat can depress the hepatocyte apoptosis of SAP rats.The mechanisms may be related to the inhibition of NE and oxygen radicals,thus up-regulating the ratio of bcl-2/bax.
Key words:
Sivelestat; Pancreatitis; Liver injury; Apoptosis
Publication Year: 2012
Publication Date: 2012-06-08
Language: en
Type: article
Access and Citation
AI Researcher Chatbot
Get quick answers to your questions about the article from our AI researcher chatbot