| Aim Diabetic nephropathy is increasingly considered as an inflammatory disease characterized by leukocyte infiltration in the renal tissues at every stage in the development and progression of the disease. Chemokines recruit the special subpopulations of inflammatory cells to the local renal tissues. Monocyte chemoattractant protein-1 (MCP-1) has been identified as having a key role in monocyte/macrophage (M/M) recruitment in animal models of diabetic nephropathy, as well as in renal biopsies from patients with type 1 and 2 diabetes. Infiltrated M/M released various substances such as lysosomal enzyme, nitric oxide, reactive oxygen mediators or transforming growth factor-β, which are essential mediators of renal damage, leading to the hypertrophy and proliferation of renal instinct cells, accumulation of extracecullar matrix, with or without fibrosis of tubuloinstertitium, and eventually resulted in glomerular sclerosis. Thiazolidinediones (TZDs) are a class of anti-diabetes drugs that improve the insulin sensitivity and act as selective and potent agonists of peroxisome proliferators-activated receptor-γ. TZDs also have been reported to protect against diabetic kidney injury through various mechanisms, such as reducing blood glucose, lowering the blood pressure, improvement of endothelial function, antiproliferative action and inference of the rennin-angiotensin system and so on. It was reported that TZDs attenuated the IL-1-mediated increase in the expression of IL-6 and tumor necrosis factor-α, and the stretch-induced increase in monocyte chemoattractant activity, by decreasing nuclear factor-κB activation and MCP-1 production in renal mesangial cells. Another possible mechanism of the renoprotective effect of TZDs is the attenuation of oxidant injury at the kidney level. This experiment was designed to investigate the renoprotective effects of rosiglitazone (one anti-diabetic drug of the TZDs) and its influence on the urinary MCP-1 excretion and the expression of MCP-1 in the renal tissues of streptozocin (STZ)-induced diabetic rats and to analyze whether its renoprotective effect is related to the inhibition of inflammatory reaction in local renal tissue.Methods 24 Wistar Rats were assigned into normal control group (group C, n=8), STZ-induced diabetes mellitus group (group D, n=8) and rosiglitazone (5mg?kg-1?d-1) treatment group (group R, n=8). Each rat in groups D and groups R received an intraperitoneal injection of STZ (65 mg/kg; Sigma Chemical, St. Louis, MO) in 0.1mol/L citrate buffer (pH 4.3) after a 24-hour fasting. 48 hours later, blood was harvested from vena caudalis to assess the blood glucose. Animals with fasting blood glucose more than 16.7mmol/L were considered diabetic. Since the modeling was completed for 1 week, rosiglitazone (5mg?kg-1?d-1) in group R or 0.9% saline in group C and D were administered via oral gavage once daily for 8 weeks. The blood was obtained from vena caudalis for the measurement of blood glucose at the second, 4th and 8th week. At the 8th week, 24h urine was collected and the urinary excretion levels of albumin (ALB), retinal-binding protein (RBP) and MCP-1 were examined, then the urinary excretion rates of the three parameters were calculated. When the rats were killed at the 8th week, femoral arterial blood was drawn simultaneously for testing the glycosylated hemoglobin A1c (HbA1c). After animals were sacrificed, the left kidney was used to calculate kidney hypertrophy index and a little part of the fresh right kidney cortices were stored for electron microscopic measurement and the rest of the kidney were stored in the liquid nitrogen using for the reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR. Photodensity ratio was used to semiquantitative determine the levels of transcript MCP-1 relative to the control transcript GAPDH in RT-PCR and the comparative ??Ct method was applied to comparative quantitative determine the gene in Real-time PCR.Results①At the 2nd, 4th and 8th week, the peripheral blood glucose levels of groups D and R were significantly higher compared with those of group C at the same period (P<0.01). The HbA1c of group D or R was much higher than it of group C, however, there was no significance between the values of group D and group R.②At the 8th week, not only the urinary excretion rates of ALB, RBP and MCP-1 (P<0.01), but also the relative kidney index were markedly increased in groups D and R compared with those in group C. However, the parameters above in group R were much lower than those in group D (P<0.01). In addition, the urinary excretion of MCP-1 was positively correlated to the urinary ALB excretion(r=0.945,P<0.01), the urinary RBP excretion(r=0.879,P<0.01) and kidney/body weigh(tr=0.934,P<0.01).③The observation of the electronic microscope: the thickness of GBM, the width of epithelial foot processes and mesangial region were normal in group C. Compared to normal control, the GBM was thickened partly with some epithelial cells foot processes fused, the ultrastructure of glomeruli and blood capillary were ambiguity, and the mesangial cells swelled and the extracellular matrix expanded. After treatment with rosiglitazone, the histobiological changes were much lighter in group R. The GMB was uniform in general and a little of the foot processes fused together.④Both the results of semi-quantitive and the comparative quantitive PCR showed that in comparison with group C, the expression of MCP-1mRNA was significantly up-regulated in group D and group R (P< 0.05or P<0.01), however, treatment with rosiglitazone could decrease the expression of MCP-1 in the renal tissues (vs. D, P< 0.05or P<0.01).Conclusions Rosiglitazone has a renoprotective effect through down-regulating the over-expression of MCP-1 in local renal tissues and reducing urinary excretion of MCP-1 in STZ-induced diabetic rats, which is independent on its effect on glycemic control.
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