肝素和高糖对人腹膜间皮细胞合成细胞外基质的影响及可能机制  

Effect and mechanism of heparin and high concentration glucose on matrix biosynthesis in cultured human peritoneal mesothelial cells

作　　者：于青[1] 黄振飞[1] 刘军[1] 姚建[1] 

机构地区：[1]上海市第一人民医院肾内科,200080

出　　处：《上海医学》2003年第11期808-810,共3页Shanghai Medical Journal

摘　　要：目的　探讨肝素和高浓度葡萄糖对体外培养的人腹膜间皮细胞 (HMC)合成细胞外基质 (ECM )的影响 ,肝素和高糖之间的相互作用及其可能的机制。方法　采用酶联免疫吸附法 (ELISA法 )检测细胞培养上清液的纤维连结蛋白(FN)、Ⅰ型胶原 (COLⅠ )、转移生长因子 (TGF) β1含量 ;采用免疫细胞化学法检测细胞核c fos、c jun蛋白的表达。 结果　3.86 %D 葡萄糖可明显促进FN和COLⅠ的分泌 ,肝素可明显降低HMC的FN和COLⅠ的分泌 ,也可降低高糖环境下FN和COLⅠ的分泌。 3.86 %D 葡萄糖对TGF β1的分泌无明显影响 ,肝素对高糖环境下TGF β1的分泌亦无明显影响。3.86 %D 葡萄糖可促进细胞核c fos、c jun蛋白表达增加 ,肝素可减少高糖引起的c fos蛋白增加 ,但对c jun蛋白增加无明显影响。结论　高糖通过促进活化蛋白 1(AP 1,c fos/c jun)表达的增加来促进ECM分泌 ,可能是长期腹膜透析导致腹膜硬化的一个重要因素 ;肝素在高糖环境下可抑制高糖所致的AP 1(c fos/c jun)表达增加及ECM分泌 ,对保护腹膜功能可能起一定作用。Objective To study the effect and the mechanism of heparin and high concentration glucose on matrix biosynthesis in cultured human peritoneal mesothelial cells and the interaction of heparin and high concentration glucose. Methods Fibronectin and collagenⅠand TGF β 1 in supernatant were detected by ELISA. c fos and c jun protein in the nuclei were determined by immunocytochemistry. Results High concentration glucose could increase the secretion of fibronectin and collagen Ⅰ, and heparin had opposite effects as well as those secretions stimulated by high concentration glucose. High concentration glucose did not affect the secretion of TGF β 1, nor did heparin. High concentration glucose could increase the expression of c fos and c jun protein in the nuclei, and heparin could inhibit the expression of c fos protein stimulated by high concentration glucose,but not the expression of c jun. Conclusion High concentration glucose increases ECM secretion by increasing the expression of AP 1(c fos/c jun),so it may play an important role in peritoneal sclerosis during peritoneal dialysis: in the environment of high concentration glucose , heparin could inhibite ECM secretion by inhibiting the expression of AP 1(c fos/c jun), hence it may be beneficial for protecting the peritoneal function during peritoneal dialysis.

关 键 词：肝素 高糖 人腹膜间皮细胞 细胞合成 细胞外基质 腹膜硬化 腹膜透析 

分 类 号：R459.5[医药卫生—治疗学]