The Impact Of Inhibiting Ceramide Synthesis On The Renal Histopathological Changes And The Expression Of ColⅣ In Diabetic Rats

Objective:This study aims to explore the following points:1, Whether inhibiting ceramide synthesis can ameliorate renal histopathological changes in diabetic rats?2, To investigate whether inhibitor of ceramide synthesis reduces the expression of ColIV in kidney? Methods:Male Sprague-Dawley (SD) rats were randomly divided into normal contral group group (NC, n=15, fed with normal food) and diabetic mellitus model group (DM, 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 normal saline. 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 after12weeks of intervention. The fasting blood of each rat was used to determine blood glucose, serum lipid, renal function, insulin, serum ceramide, glycated hemoglobin (HbA1C). After the execution of rats, kidneys were immediately isolated and sectioned for the observation of renal histopathological changes under HE staining and PAS staining, collagen IV were detected with Western-blot. Results:1, Compared with NC group, the level of serum ceramide, serum glucose, lipid, insulin, BUN, insulin resistance indexes, HbA1C in DMC group and MTD group increased significantly (P<0.05), but the increase in DMC group was more than that in MTD group (P<0.05).2, Renal histopathological changes, BUN and glomerulosclerosis index(GSI)in DMC group and MTD group was much heavier than NC group (P<0.01), but the renal histopathological changes and glomerulosclerosis index of MTD group was lighter than that in DMC group (P<0.05).3, Compared with NC group, the renal expression of Col IV in DMC group and MTD group increased obviously (P<0.01), but the expression in MTD group was lesser than that in DMC group (P<0.05). Conclusions:1, In type2diabetic rats model, the level of serum ceramide, serum glucose, lipid, insulin, insulin resistance indexes, HbA1C are increased obviously, renal histopathological changes and renal function injury are detected, and GSI is increased.2, Myriocin which is an inhibitor of ceramide of de novo synthetic pathway was injected by intraperitoneal in type2diabetic rats model, the level of serum ceramide, BUN and lipid are reduced, GSI is decreased, the insulin sensitivity and the renal histopathological changes are improved.3, In type2diabetic rats model, the accumulation of ceramide can increase renal expression of Col Ⅳ, myriocin which is an inhibitor of ceramide of de novo synthetic pathway can lower renal expression of Col Ⅳ, prompts that the ceramide is one of the mechanisms which regulates renal expression of Col IV. Inhibit ceramide synthesis may be a new target for the treatment of diabetic nephropathy.