中文摘要：

目的探讨晚期糖基化终末产物（Advanced glycosylation end products,AGEs）对大鼠肾小管上皮细胞NRK-52E组织型转谷氨酰胺酶（Tissue transglutanunase,tTG）mRNA表达及其对细胞外基质（Extracellular matrix,ECM）降解的影响。方法体外培养NRK-52E细胞,分别用体外合成的不同浓度的糖化牛血清白蛋白（AGE-BSA）及未经糖化的牛血清白蛋白（BSA）处理48h,ELISA法检测细胞培养上清中纤维连接蛋白（Fibronectin,FN）和Ⅳ型胶原蛋白（TypeⅣcollagen,ColⅣ）含量,RT-PCR检测细胞tTG mRNA的表达。结果与BSA组比较,50～200mg/LAGE-BSA组细胞上清中FN含量明显增加（P〈0.01）,25～100mg/L AGE-BSA组细胞上清中ColⅣ含量明显增加（P〈0.05）;AGE-BSA（50～400mg/L）可不同程度地刺激细胞tTG mRNA表达的增加（P〈0.05）;tTG mRNA表达增加与FN、ColⅣ分泌增多呈正相关（r值分别为0.911和0.872）。结论 AGEs能诱导大鼠近端肾小管上皮细胞tTG mRNA的表达,引起ECM主要成分FN和ColⅣ含量增加,提示tTG可能在AGEs引起的ECM积聚过程中,起到抑制ECM蛋白降解的作用,进而参与糖尿病肾病的病理过程。

英文摘要：

Objective To investigate the effect of advanced glycosylation end products（AGEs）on the expression of tissue transglutaminase（tTG）mRNA in rat proximal tubular epithelial cells NRK-52E as well as on the degradation of extracellular matrix（ECM）.Methods NRK-52E cells were cultured in vitro,then treated with various concentrations of AGE-BSA and BSA synthesized in vitro for 48 h respectively.The fibronectin（FN）and type Ⅳ collagen（Col Ⅳ）contents in supernatant of cell culture were determined by ELISA,while the expression of tTG mRNA by RT-PCR.Results Compared with those treated with BSA,the FN content in supernatant of cells treated with 50 ～ 200 mg /L AGE-BSA increased significantly（P 0.01）,and the Col Ⅳ content in those treated with 25～100 mg /L AGE-BSA increased significantly（P〈0.05）.The increase of expressed tTG mRNA was positively related to the increase of secreted FN（r = 0.911）and Col Ⅳ（r = 0.872）.Conclusion AGEs induced the expression of tTG mRNA in rat proximal tubular epithelial cells and increased the contents of FN and Col Ⅳ as major components of ECM,indicating that tTG might inhibit the degradation of ECM during cumulation of ECM caused by AGEs and be involved in the pathogenesis of diabetic nephropathies.