- 作者：Furong Wang ; Mei Li ; Lin Cheng ; Tingguo Zhang ; Jianting Hu ; Mingfeng Cao ; Jiajun Zhao ; RuiChen Guo ; Ling Gao ; Xiumei Zhang
- 关键词：Cilostazol ; Diabetic nephropathy ; ICAM-1 ; MCP-1 ; NF-κ ; B ; VCAM-1 ; VEGF
- 刊名：Life Sciences
- 出版年：2008
- 出版时间：19 December 2008
- 年：2008
- 卷：83
- 期：25-26
- 页码：828-835
- 全文大小：904 K
AimsAn inflammatory reaction is commonly found in the pathogenesis of diabetic nephropathy (DN). Cilostazol, a type 3 phosphodiesterase (PDE) inhibitor, has been previously reported to be anti-inflammatory, independent of an anti-platelet property. In the present study, we evaluated the hypothesis that cilostazol has protective effects on diabetic nephropathy by modulating the inflammatory process.Main methods
Cilostazol was administered (27 or 9 mg kg− 1 d− 1) to streptozotocin (STZ)-induced diabetic rats for eight weeks. We studied the kidney expression of vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 by immunofluorescence, western blotting and real-time PCR. The renal monocyte chemoattractant protein (MCP)-1 and vascular endothelial growth factor (VEGF) levels were examined by ELISA. The nuclear factor (NF)-κB-DNA binding activity was assessed by electrophoresis mobility shift assay (EMSA).
Key findings
Our results showed cilostazol inhibited diabetes-induced hypertrophy of the glomeruli and infiltration of inflammatory cells, as well as the increase in the VCAM-1 and ICAM-1 mRNA and protein expression, and MCP-1 and VEGF contents in the kidneys. Consistent with these findings, cilostazol attenuated the enhanced activation of NF-κB in diabetic rats.
Significance
These results demonstrate that the renoprotective effects of cilostazol may be mediated by its anti-inflammatory actions, including inhibition of NF-κB activation and the subsequent decrease in proinflammatory factors, such as VCAM-1, ICAM-1, MCP-1 and VEGF expression in kidneys of diabetic rats.