| Background:Diabetic kidney disease (DKD), is one of the most serious complications of diabetes, as the incidence of diabetes increased, DKD is increasingly becoming the major cause of the end-stage renal disease. Now DKD is considered to be a multi-factorial disease, involving the pathogenesis of metabolism, inflammation, endothelial function disorder and others. Visfatin(VF) is a member of adipocytokines discovered in recent years, also called pre-B-cell colony enhancing factor(PBEF) and nicotinamide phosphoribosyltransferase (Nampt). Studies have shown that the biological function of VF is complex, which is closely related to lipid metabolism, energy cycle and inflammation. It has also been reported that in metabolic syndrome and a variety of acute and chronic inflammatory diseases, the plasma level of VF increased. VF may be involved in the pathogenesis of DKD. Further researches on VF may provide new directions of the treatment for DKD.Objective:To observe the metabolitic change in the DKD animal model db/db mice and renal damage. To evaluate the expression of VF and whether PTN intervention can affect its expression in kidney of db/db mice. To reveal the possible pathogenic mechanism of VF in DKD.Methods:C57 BKS db/db mice and db/m mice had been divided into three groups:db/m+NS, db/db+NS, and db/db+PTN after getting the baseline data. The mice were sacrificed at 8,12,16 and 20 weeks old and the serum, urine, and kidney were collected. Tests had been made on glucose, lipids, insulin, HOMA-IR, creatinine in serum; VF, resistin, RBP4 in serum; albumin, NAG, urinary sodium excretion fraction in urine. VF in kidney were measured by immunochemistry and Western blot, resistin in kidney were measured by Western blot.Results:1、In db/db+NS group, the body weight, serum glucose, TC, HOMA-IR and serum resistin at 8w,12w,16w and 20w were significantly increased (p<0.05) compared with db/m+NS group; TG at 8w were significantly increased (p<0.05); insulin at 8w,12w and 16w were increased significantly (p<0.05); serum VF at 8w,12w,16w and 20w were elevated, and at 8w and 12w were significantly increased (p<0.05); serum RBP4 at 16w and 20w were increased, and at 20w were significantly increased (p<0.05). In db/db+PTN mice, the body weight, serum glucose, TG, serum VF did not change compared with db/db+NS group; TC at 12w significantly decreased (p<0.05); insulin at 12w,16w and 20w decreased; HOMA-IR at 12w and 16w decreased, and at 16w significantly decreased (p<0.05); serum resistin at 8w,12w,16w and 20w decreased; serum RBP4 at 16w and 20w decreased, and at 20w significantly decreased (p<0.05). 2、In db/db+NS group, the urine volume at 8w,12w,16w and 20w increased compared with db/m+NS group; urinary albumin concentration and 24h urinary albumin at 8w,12w,16w and 20w were elevated, and at 8w,16w and 20w were significantly increased(p< 0.05); serum creatinine did not change; urinary NAG and urinary sodium excretion fraction at 16w and 20w were elevated. In db/db+PTN mice, urine volume, serum creatinine, NAG did not change compared with db/db+NS group; urinary albumin concentration and 24h urinary albumin at 12w decreased; urinary sodium excretion fraction at 16w and 20w decreased. 3-. VF was detected in the glomerular and tubule of kidney, mainly distributed in the cytoplasm of the proximal tubular epithelial cells. It was increased in kidney in db/db mice compared with db/m mice (the positive IHC areas: 8w:2.216±1.036 vs 8.968±5.493, p<0.05; 12w:4.138±3.001 vs 8.333±3.097; 16w:2.122±1.106 vs 6.377±2.459, p<0.05; 20w:2.419±2.871 vs 4.502± 1.386. relative optical density in WB:8w:1.000±0.150 vs 1.221±0.045, p <0.05; 12w:1.107±0.126 vs 1.239±0.066; 16w:0.973±0.072 vs 1.157±0.061, p<0.05;20w:1.097±0.185 vs 1.157±0.339). In db/db+PTN group, the expression of VF had no significant change (the positive IHC areas:8w:8.968 ±5.493 vs 8.765±4.983; 12w:8.333±3.097 vs 8.279±4.100; 16w:6.377± 2.459 vs 6.923±2.176; 20w:4.502±1.386 vs 4.071±1.261. relative optical density in WB:8w:1.221±0.045 vs 1.240±0.085; 12w:1.239±0.066 vs 1.398 ±0.308; 16w:1.157±0.061 vs 1.164±0.188; 20w:1.157±0.339 vs 1.166± 0.254).4.. Resistin expressed in the kidney of mice. Its expression increased with age in db/db mice. The expression of resistin was increased in kidney in db/db mice at 16w compared with db/m mice(relative optical density in WB: 8w:1.000±0.053 vs 0.991±0.032; 16w:1.168±0.049 vs 1.072±0.058, p< 0.05). In db/db+PTN group, the expression of resistin was decreased at 16w compared with db/db+NS group(relative optical density in WB:8w:0.991± 0.032 vs 1.025±0.114; 16w:1.168±0.049 vs 1.072±0.058, p<0.05).Conclusion:1、Db/db mice showed obesity, hyperglycemia, hyperlipidemia, insulin resistance and kidney damage. PTN may improve the hyperlipidemia and insulin resistance.2、In db/db mice, the level of VF, resistin, RBP4 in serum were elevated compared with control group. PTN may improve the elevated level of resistin and RBP4.3、VF expressed in kidney, and the level of VF in kidney was elevated compared with control group. PTN intervention did not affect the expression of VF.4、Resistin expressed in kidney, and the level of resistin in kidney was elevated compared with control group. PTN may improve the elevated expression of resistin in kidney. |
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