The Impact Of Inhibiting Ceramide Synthesis On Endoplasmic Reticulum Stress-induced Hepatic Steatosis In Diabetic Rats

Objective:This study aims to explore whether inhibiting ceramide synthesis can ameliorate hepatic steatosis in type2diabetic rats by regulating the expression of endoplasmic reticulum stress markers BIP/GRP78,CHOP and SREBP1Methods:Male 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 into two groups: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 serum ceramide, glucose,HbA1C, insulin, liver function and blood fat biochemical indicators. After the execution of rats, livers were immediately isolated and sectioned for the observation of the expression of endoplasmic reticulum stress markers BIP/GRP78,CHOP,SREBP1with western-blot.Results:1, Compared with NC group, the level of serum ceramide, glucose, lipid, insulin resistance indexes in DMC group and MTD group increased significantly (P<0.05), but the increase in MTD group was lesser than that in DMC group (P<0.05)2, Compared with NC group, liver function (level of ALT and AST) in DMC group and MTD group was seriously impaired (P<0.05), but the impairment in MTD group was relieved compared with DMC group (P<0.05). Liver weight and liver index in DMC group and MTD group was higher than that in NC group (P<0.05), but that was decreased in MTD group compared with DMC group (P<0.05). In addition,hepatic steatosis in DMC group and MTD group was more serious than that in NC group, and the hepatic steatosis of MTD group was relieved compared with DMC group.These was observed by liver histopathological method.3, Compared with NC group,the expression of hepatic BIP protein was decreased in DMC group (P<0.05).Besides, the level of BIP protein was increased in MTD group compared with DMC group (P<0.05).But,there were no statistical difference bet ween NC group and MTD group (P>0.05)4, The expression of hepatic CHOP protein in DMC group and MTD group were significantly higher than that in NC group (P<0.05).There were no significant difference between DMC group and MTD group (P>0.05),but the MTD group appeared a downward trend.5, Compared with NC group,the expression of hepatic SREBP1protein was increased in DMC group (P<0.05).And there was a downward trend in MTD group compared with DMC group,but the difference was not statistically significant (P>0.05).Conclusions:1,Ceramide accumulation may be related to the pathogenesis of NAFLD by decreasing the level of BIP and increasing the level of CHOP,SREBP1.2,Inhibition of ceramide synthesis may ameliorate NAFLD in type2diabetic rats by regulating the expression of endoplasmic reticulum stress markers BIP,CHOP,SREBP1.