糖基化终末产物对肾小球系膜细胞表达纤溶酶原激活物抑制物1的影响  

Effects of glycated protein on the expression of plasminogen activator inhibitor 1 of cultured human mesangial cells

作　　者：邓义斌[1,2] 陈香美[1,2] 叶一舟[1,2] 李才 王凡 

机构地区：[1]解放军总医院肾病科解放军肾病中心 [2]白求恩医科大学应用基础医学研究所

出　　处：《中华医学杂志》1997年第9期672-675,共4页National Medical Journal of China

基　　金：国家自然科学基金;优秀中青年人才基金;军队"九五"重点课题基金

摘　　要：探讨非酶促糖基化终末产物是否影响肾小球系膜细胞降解肾小球细胞外基质的丝氨酸蛋白酶－纤溶酶原激活物抑制物１（ＰＡＩ－１）基因表达和生物学活性。方法用体外制备的非酶促糖基化牛血清白蛋白（ＡＧＥ－ＢＳＡ）作用人肾小球系膜细胞２４小时和４８小时，观察对细胞增殖、纤维连接蛋白分泌、ＰＡＩ－１基因表达和生物学活性的作用。结果ＡＧＥ－ＢＳＡ抑制肾小球系膜细胞增殖，促进纤维连接蛋白分泌，上调ＰＡＩ－１生物学活性。ＡＧＥ－ＢＳＡ作用系膜细胞２４小时后，ＰＡＩ－１基因表达显著增加（０．６５％±０．０８％，对照０．４５％±０．０６％，Ｐ＜０．０５）；４８小时后ＰＡＩ－１基因表达增加更趋显著（０．９２％±０．１０％，对照０．５１±０．０８，Ｐ＜０．０１）。结论非酶促糖基化终末产物增加肾小球系膜细胞ＰＡＩ－１基因表达和生物学活性，参与了肾小球细胞外基质积聚和肾小球硬化的病理生理过程。bjective To investigate whether nonenzymatic glycated end products (AGEs) have effects on the expression and bioactivity of plasminogen activator inhibitor 1 (PAI 1), one of the seripin proteinases, which lead to extracellular matrix (ECM) degradation in cultured human mesangial cells. Methods Human mesangial cells (HMC) were cultured. Cell proliferation, fibronectin production, mRNA expression and bioactivity of PAI 1 were determined after exposure to AGE BSA for 24 hours and 48 hours in vitro. Results HMC stimulated by AGE BSA exhibited inhibition in HMC proliferation, increase in fibronectin production, and PAI 1 bioactivity. These changes were pronounced with prolongation of experimental time. PAI 1 mRNA expression increased significantly at 24hr (0.45%±0.06% vs 0.65%±0.08%, P <0.05), however more marked increase of PAI 1 mRNA expression at 48hr (0.51± 0.08% vs 0.92±0.10%, P <0.01). Conclusions Increase of mRNA expression and bioactivity of PAI 1 induced by AGEs decreased ECM degradation and play an important role in the pathogenesis of ECM accumulation and glomerulosclerosis.

关 键 词：肾小球系膜细胞 PAI-1 肾小球疾病 AGE-BSA 

分 类 号：R692.602[医药卫生—泌尿科学]