【摘要】 目的:观察糖基化终末产物(AGEs)对大鼠肾系膜细胞纤溶酶原激活物抑制物-1(PAI-1)表达的影响及其与细胞外基质(ECM)成分含量的关系。方法:体外培养正常大鼠肾系膜细胞,分别用糖化牛血清白蛋白(AGEs)及未经糖化的牛血清白蛋白(BSA)处理,以常规培养的肾系膜细胞作为对照,检测不同时间、不同浓度AGEs对纤维连接蛋白(FN)、Ⅳ型胶原、PAI-1表达的影响。MTT法检测AGEs对系膜细胞增殖的作用,ELISA测定条件培养基中FN、Ⅳ型胶原及PAI-1蛋白含量,逆转录聚合酶链式反应(RT-PCR)检测系膜细胞PAI-1mRNA的表达。结果:与相应浓度的BSA比较,AGEs(0-200mg/L)对系膜细胞增殖无明显影响,但可不同程度地刺激系膜细胞FN、Ⅳ型胶原、PAI-1蛋白的产生。RT-PCR检测显示,给予AGEs(100mg/L)的系膜细胞PAI-1mRNA的表达明显增加(P<0.01)。结论:AGEs促进系膜细胞PAI-1的表达,提示AGEs通过上调PAI-1的表达而减少细胞外基质降解,可能是糖尿病肾病细胞外基质积聚的原因之一。更多还原

【Abstract】 AIM: To investigate the effects of advanced glycation end products (AGEs) on the expression of plasminogen activator inhibitor-1 (PAI-1) in rat mesangial cells and its relationship with extracellular matrix accumulation. METHODS: Rat mesangial cells were treated with AGE-modified bovine serum albumin or native bovine serum albumin. Normal mesangial cells without any treatments were used as control. Fibronectin (FN), collagen Ⅳ, PAI-1 protein contents were detected by ELISA. PAI-1 mRNA was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: AGEs (0-200 mg/L) did not influence mesangial cells proliferation, but stimulated FN , collagen IV and PAI-1 contents in mesangial cell cultured medium in different degrees. AGEs also increased PAI-1 mRNA expression. CONCLUSION: AGEs increase the expression of PAI-1 in rat mesangial cells. AGEs may reduce ECM degradation through increasing PAI-1 expression, which may be one of the mechanisms of ECM accumulation in diabetic nephropathy.更多还原