己酮可可碱对高糖时人肾小球系膜细胞单核细胞趋化蛋白-1表达的影响

Effect of pentoxifylline on high glucose-induced expression of MCP-1 mRNA in human mesangial cells

目的探讨高糖对人肾小球系膜细胞单核细胞趋化蛋白1(monocyte chemoattractant protein-1,MCP-1)表达的影响及己酮可可碱(pentoxifylline,PTX)对其干预作用。方法将培养的人肾小球系膜细胞分为6组:正常对照组、高糖组、甘露醇组、PTX甲组、PTX乙组、PTX丙组,分别在24、48和72 h采用RT-PCR法和ELISA法检测PTX对高糖条件下系膜细胞内MCP-1mRNA及蛋白、细胞外基质纤维连接蛋白(fi-bronectin,FN)表达的影响。结果高糖组人肾小球系膜细胞MCP-1mRNA及蛋白、FN的表达较正常对照组明显增加(P<0.01);己酮可可碱各组比高糖组有明显下降(P<0.01);不同浓度的己酮可可碱对高糖诱导的系膜细胞MCP-1的表达抑制程度不同(P<0.05)。结论己酮可可碱可抑制高糖诱导的人肾小球系膜细胞MCP-1的表达以及FN的分泌,呈时间、剂量依赖关系,己酮可可碱可能对糖尿病肾病的防治起到有益的作用。

【Objective】 To investigate the effect of high glucose on expression of MCP-1mRNA in human mesangial cells and the intervention of pentoxifylline.【Methods】 Cultured human mesangial cells were divided into six groups ： normal control group（5 mmol/l G）,high glucose group（30 mmol/l G）,mannitol group（5 mmol/l G with 25 mmol/l mannitol）,and pentoxifylline groups（high glucose 30mmol/l G with pentoxifylline 0.03 mg/mL,0.1 mg/mL,0.3 mg/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.【Results】 The mRNA and protein expression of MCP-1 and fibronectin increased significantly in high glucose（P 0.01）.However,pentoxifylline inhibited the expression（P 0.01）.The different concentration of pentoxifylline on high glucose induced expression of MCP-1 in human mesangial cells to varying degrees（P 0.05）.【Conclusion】 Pentoxifylline has an intrinsic 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 reasonable application of pentoxifylline may be helpful in preventing and treating diabetic nephropathy.