Effects Of Shenling Baizhu San On The Endocrine And Exocrine Function Of Pancreas In Mice With High Fat Diet

Objective:To observe the effect of Shenling Baizhu San on the endocrine function and exocrine function of pancreatic tissue in high fat diet mice.Method:The mice were adapted for a week and then randomly divided into control group and high-fat diet group,which were fed with normal diet and high-fat diet,respectively.After two weeks,the mice in high fat diet group were then divided into model group and Shenling intervention group randomly.The mice in normal group and model group were given normal saline and the mice in Shenling group were given Shenling Baizhu San at the dose of 28g/kg by daily gavage.Body weight and blood glucose level were recorded.After 14 weeks,intraperitoneal injection of glucose tolerance test(IPGTT)and intraperitoneal injection of insulin resistance test(IPITT)were performed.Small Animal Physiological Monitoring System(CLAMS)were applied to measure the energy metabolism of mice at the 16th week of the experiment by recording food consumption,oxygen consumption,carbon dioxide production,Respiratory exchange ratio and energy consumption for continuous 24 hours.At the end of the experiment,plasma was collected,and the levels of insulin,glucagon,somatostatin,and pancreatic polypeptide were determined by ELISA.Plasma triglyceride,cholesterol,LDL-C,free fatty acids and pancreatic amylase,pancreatic lipase levels and pancreatic tissue triglyceride,cholesterol,free fatty acid content were detected by biochemical methods.Protein expression was determined by Western blot and immunofluorescence,and mRNA expression was determined by RT-PCR to quantify or semi-quantify levels of insulin,somatostatin,pancreatic polypeptide,NF-?B,IL-6,TNF-a,etc.Pancreatic tissues were assayed for triglyceride,cholesterol,and free fatty acid levels by biochemical methods.Results:(1)Body weight and blood glucose:Compared to the normal group,body weight and blood glucose were significantly increased in the model group.Treatment with Shenling Baizhu San can significantly reduce the body weight and blood glucose induced by high fat diet.(2)'CLAMS data showed that the food consumption of mice in the model group was significantly lower than that of the normal group.The respiratory quotient of the model group mice was lower than that of the normal group,indicating that the mice in the model group mainly consum lipids and their energy consumption was lower than that of the normal group.Shenling group showed a trend to increase food intake and recover the energy metabolism compared to model group.(3)IPITT and IPGTT experiments and plasma lipid levels showed that the insulin sensitivity and glucose tolerance were decreased in model group compared to normal group.Cholesterol and LDL-C?FFA levels in model group were higher than those in normal group.Compare to the model group,shenling group showed a tendency to decrease plasma lipid levels and improve glucose tolerance and insulin sensitivity and therefore,improvelipid and glucose metabolism.(4)Pancreatic lipid infiltration:HE staining and oil red O staining showed that there were more adipose vacuoles in the acinar cells,islet cells and interlobular tissues in the model group than those in the normal group.The content of triglyceride,cholesterol and free fatty acid in pancreatic tissue supernatant was higher than that in normal group.The Shenling group can reduce triglyceride and free fatty acid levels in pancreatic tissues and reduce pancreatic fat infiltration.(5)Pancreatic Tissue Inflammation:The mRNA levels of IL-6 and TNF-? in the mice of the model group were moderately increased compared with the normal group,although not significantly.The Shenling group showed a tendency to decrease the mRNA levels of IL-6 and TNF-a.The expression of NF-?B protein in the model group mice was higher than that the normal group.The Shenling group could reduce the expression of NF-?B protein.(6)Pancreatic endocrine conditions:The insulin content in the mouse model group was increased compared with the normal group,and the ? cell mass(BCM)of the pancreas was increased compared with the normal group.Shenling Baizhu San can reduce the plasma insulin content and ?cell mass(BCM)in pancreas;The plasma glucagon levels in the mice of the model group had a tendency to increase compared with the normal group,Shenling Baizhu San has the tendency of decreasing plasma glucagon content.The level of somatostatin in plasma and pancreatic tissue of mice in the model group was not different from that in the normal group,Shenling Baizhu San can increase somatostatin content;The pancreatic polypeptides in the plasma and pancreatic tissue of mice in the model group were increased compared with the normal group.Shenling Baizhu San can increase the pancreatic polypeptide content in plasma and pancreatic tissue of high-fat fed mice.(7)Pancreatic exocrine conditions:The level of amylase lipase in the pancreas of the model group was lower than that of the normal group.The pancreatic lipase in the model group had a tendency to decrease compared with the normal group,but there was no statistical significance because of the variance in the group.The Shenling group has a tendency to increase the secretion of pancreatic amylase and pancreatic lipase.Conclusion:The mice pancreas showed pancreatic fat infiltrates upon a long-term high-fat diet,meanwhile,the pancreas endocrine function and exocrine function were damaged.Shenling Baizhu San has a protective effect against high fat diet,which may be related to the improvement of pancreatic fat deposits and reduction of inflammation in pancreatic tissue.