Effect Of Pentoxifylline On High Glucose-induced Expression Of MCP-1 MRNA In Human Mesangial Cells

BackgroundDiabetic nephropathy is one of the most important diabetic complications,and it is also the significant reason of End-stage renal disease in Europe and America and other developed countries.,which is caused by the pathologic change of diabetic microvascular.However,the pathogenesis of diabetic nephropathy is unclear yet,it is generally caused by many factors combined action,which including oxidative Stress, proteinkinaseC,Polyol Pathway and advanced glycation end products.Diabetic nephropathy is considered as an metabolic disease in the past,but more and more researchs indicate inflammatory play important roles in the pathology of diabetic nephropathy.Monocyte chemoattractant protein-1 (MCP-1) as a member of the chemokine's CC sub-family is involved in the recruitment of all kinds of inflammatory cells especially monocytes and macrophages into the pathological sites,Leading to the development of diabetic nephropathy. Pentoxifylline is a phosphordiesterase inhibitors, which can increase cAMP in cells, improve the function of haemodynamics, immunosuppression, anti-fibrosis and so on.ObjectiveTo investigate the effect of high glucose on expression of MCP-1 mRNA in human mesangial cells and the intervention of Pentoxifylline.MethodsCulture human mesangial cells were divided into six groups:normal glucose group (5mmol/l glucose),high glucose group (30mmol/l glucose),mannitol group (5 mmol/1 glucose with 25mmol/l mannitol),and Pentoxifylline groups (high glucose 30mmol/l glucose with pentoxifylline 0.03mg/ml,0.1mg/ml,0.3mg/ml) were established for 24,48,72 hours.The mRNA and protein of MCP-1 were measured by RT-PCR and ELISA, and fibronectin in supernatant was detected by ELISA.ResultsThe expression of MCP-1 mRNA increased significantly in high glucose group(P＜0.01), while that in normal glucose group was weak. However, Pentoxifylline inhibited the expression (P<0.01), effect of Pentoxifylline on expression of MCP-1 mRNA in cultuered human mesangial cells at 48h was the most obvious. Suppression effect increased significantly with the increase of the concentration of PTX (P＜0.05). Effect of Pentoxifylline on expression of MCP-1 mRNA in cultuered human mesangial cells at 72h slightly declined comparing to that at 48h..The concentration of MCP-1 and fibronetin in supermatant of human mesangial cell at 24,48,72 hours increased significantly in high glucose(P<0.01).The expression at 48h was the most obvious,while that at 72h decresed. There was no significant difference beween mannitol group and normal glucose group (P>0.05). The concentration of MCP-1 and fibronection in Pentoxifylline groups delinced significantly in compared to high glucose group (P<0.05).,and suppression effect increased significantly with the increase of the concentration of PTX (P＜0.05).The result indicated inhibiting effects were in a concentration and time dependent manners in Pentoxifylline concentration range of 0.03-0.3mg/ml,and that at 48h was the most obvious.ConclusionsPentoxifylline has an intrintic capability of inhibiting the effect of high glucose on expression of MCP-1 in human mesangial cells and these effects are in a Pentoxifylline concentration and time dependent manners. The resanable application of Pentoxifylline may be helpful in preventing and treating diabetic nephropathy.