A Study Of The Impact Of Inhibiting Ceramide Synthesis On The Hepatic Steatosis In Diabetic Rats

ObjectiveThis study aims to explorer the following points:1, Whether inhibiting ceramide synthesis can ameliorate hepatic steatosis in diabetic rats?2, To investigate whether inhibitor of ceramide synthesis ameliorates hepatic steatosis by regulating hepatocyte apoptosis?MethodsMale Sprague-Dawley (SD) rats were randomly divided into normal contral (NC) group (n=15, fed with normal food) and diabetes mellitus (DM) model group(n=45, fed with high-sugar and high fat food). Four weeks later, DM model group were injected with low dose streptozotocin (STZ30mg/Kg) to establish experimental diabetic rats model. Then, the diabetic rats were randomly subdivided into2groups:diabetic mellitus control group (DMC group), and myriocin treated diabetic group (MTD group). MTD group were intraperitoneally injected with myriocin0.3mg/Kg QOD, the others were intraperitoneally injected with the same amount of solvent. Diabetic rats fed with a high sugar and high fat food, and the normal control group rats were fed with normal food.All rats were killed after14weeks of intervention. The fasting blood of each rat was used to determine glycated hemoglobin(HbA1c), serum ceramide, insulin, liver function and blood fat biochemical indicators. After the execution of rats, livers were immediately isolated and sectioned for the observation of liver histopathological changes under HE staining and hepatic steatosis under Sudan IV staining. Signal molecular Bcl-2and Bax protein were detected with western-blot.Results1, Compared with NC group, the level of serum ceramide, glucose, lipid, Insulin resistance indexes in DMC group and MTD group increased significantly (P<0.005), but the increase in MTD group was lesser than that in DMC group (P<0.005)2, Compared with NC group, Liver function (level of ALT and AST) in DMC group and MTD group was seriously damaged (P<0.005), but the damage in MTD group was lighter than in DMC group (P<0.005) Liver weight and liver index in DMC group and MTD group DM was heavier than in NC group (P<0.005), but the liver weight and liver index in MTD group was lighter than in DMC group (P<0.005)3, Hepatic steatosis in DMC group and MTD group was much heavier than NC group, but the hepatic steatosis of MTD group was lighter than in DMC group (P<0.005)4, Compared with NC group, the expression of hepatic Bax protein in DMC group and MTD group increased obviously (P<0.005), but the expression in MTD group was lesser than that in DMC group (P<0.005)。 Meantime, the expression of hepatic Bcl-2protein in DMC group and MTD group declined obviously (P<0.005), but the expression in MTD group was more than that in DMC group (P<0.005)CONCLUSIONS:1, In type2diabetic rats model, level of serum ceramide, lipid and insulin resistance index are increased, and hepatic steatosis is detected.2, Myrioicin which is an inhibitor of ceramide of de novo synthetic pathway renduces level of serum ceramide, and improve lipid and insulin sensitivity.3, Myrioicin which is an inhibitor of ceramide of de novo synthetic pathway ameliorates hepatic steatosis and liver function.4, Myrioicin which is an inhibitor of ceramide of de novo synthetic pathway regulates the expression Bcl-2and Bax protein, which contribute to the development of hepatic steatosis.