| Part one:The mechanism of myosin light chain kinase in diabetic nephropathyObjective:Renal hemodynamics is modulated by the relaxation and contraction of renal arteries. The vasomotoricity is due to the relaxation and contraction of vascular smooth muscle. In addition, myosin light chain kinase (MLCK) is involved in the process of relaxation and contraction of vascular smooth muscle. The aim of this study is to investigate the mechanism of MLCK in diabetic nephropathy.Methods:Diabetes was induced by a caudal vein injection of streptozotocin. The diabetic rats were then randomly divided into diabetic group and insulin group. The rats were sacrificed after eight weeks. Blood glucose, body weight, and kidney weight/body weight were measured. The expression levels of MLCK, phosphorylated myosin light chain (p-MLC), and total MLC in the kidney were determined.Results:Body weight was significantly decreased, as well as blood glucose, kidney weight/body weight and creatinine clearance (Ccr) were significantly increased in diabetic rats compared with controls. Insulin treatment could significantly ameliorate those values. In addition, the expression levels of MLCK and p-MLC were significantly reduced in the kidney of diabetic rats compared with control group. However, no differences in the expression level of total MLC between the two groups were found. Insulin group showed significantly increased levels of MLCK and p-MLC compared with diabetic group. However, insulin treatment showed no significant effects on the expression level of total MLC.Conclusion:MLCK is involved in the mechanism of diabetic nephropathy.Part two:The mechanism of chemerin in diabetic nephropathyObjective:Chemerin is related to inflammation. In addition, inflammation plays an important role in the mechanism of diabetic nephropathy. This study aims to determine the expression of chemerin in the kidney of diabetic rats and then to analyze the association of chemerin expression with the factors related to inflammation and fibrosis.Methods:Diabetes was induced by a caudal vein injection of streptozotocin. The rats were sacrificed after eight weeks. Blood glucose, body weight, kidney weight/body weight, and urine albumin excretion (UAE) were measured. The expression levels of chemerin and ChemR23in the kidney were determined. Spearman correlation analysis was performed to analyze the association of chemerin with transforming growth factor-β1(TGF-β1), connective tissue growth factor (CTGF), tumor necrosis factor-alpha (TNF-α), and intercellular adhesion molecule1(ICAM-1).Results:Body weight was significantly decreased, as well as blood glucose, kidney weight/body weight, UAE, and Ccr were significantly increased in diabetic rats compared with controls. Diabetic rats showed significantly higher expression levels of chemerin and ChemR23compared with control group. Spearman correlation analysis indicated that chemerin expression level was positively correlated with TGF-β1, CTGF, TNF-α, and ICAM-1expression in diabetic rats.Conclusion:Chemerin and ChemR23may play important roles in the mechanism of diabetic nephropathy. Chemerin is related to inflammation and fibrosis.Part three:The effects of rosiglitazone and pioglitazone on the expression of chemerin in the kidney of diabetic ratsObjective:Thiazolidinediones could protect against renal injury and decrease the serum levels of several adipokines. The aim of this study is to determine whether rosiglitazone and pioglitazone could ameliorate diabetic nephropathy through regulating the expression of chemerin and ChemR23in the kidney of diabetic rats. Methods:Diabetes was induced by a caudal vein injection of streptozotocin. The diabetic rats were then randomly divided into diabetic group, rosiglitazone group, and pioglitazone group. The rats were sacrificed after eight weeks. Blood glucose, body weight, kidney weight/body weight, and UAE were measured. The expression levels of chemerin and ChemR23in the kidney of the four groups were examined.Results:Rosiglitazone and pioglitazone could ameliorate renal function. UAE and Ccr were significantly decreased in the two groups than diabetic group. Rosiglitazone inhibited the overexpression of chemerin in the kidney of diabetic rats. However, no significant differences in the expression of chemerin in the kidney were found between pioglitazone group and diabetic group. Furthermore, rosiglitazone and pioglitazone both decreased the overexpression of ChemR23in the kidney of diabetic rats.Conclusion:Rosiglitazone ameliorates diabetic nephropathy by reducing the expression of chemerin and ChemR23in diabetic rats. In addition, pioglitazone ameliorates diabetic nephropathy by reducing the expression of ChemR23in diabetic ratsPart four:Association of serum chemerin with diabetic nephropathyObjective:Serum levels of chemerin are elevated in patients on chronic hemodialysis. Serum chemerin is related to renal function. This study aims to determine the serum levels of chemerin in patients with diabetic nephropathy and the association of serum chemerin with other clinical characteristics.Methods:116patients with type2diabetes and38healthy controls were enrolled in this study. Patients with type2diabetes were divided into normoalbuminuria group, microalbuminuria group, and macroalbuminuria group according to UAE.Results:Serum chemerin was significantly elevated in type2diabetic patients with macroalbuminuria compared with control subjects and diabetic patients with normoalbuminuria and microalbuminuria. No differences were found in the level of serum chemerin between diabetic patients with normoalbuminuria and microalbuminuria and control subjects. In addition, there were no significant differences in serum chemerin levels between female and male patients. Serum chemerin was positively correlated with age, body mass index, systolic blood pressure, C-reactive protein, blood urea nitrogen, serum creatinine and serum triglycerides, and negatively correlated with Ccr.Conclusion:Serum chemerin levels are elevated in patients with diabetic nephropathy. Serum chemerin could serve as a serum marker for predicting and diagnosing the presence of diabetic nephropathy. |
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