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目的 :研究高血糖依赖性的糖化终末产物 (AGE)对内皮素 1(ET 1)诱导生成的作用。方法 :将牛主动脉内皮细胞 (BAECs)和糖尿病患者的红细胞共同培养 ,以诱导ET 1的产生。Western blot法分析红细胞的羧甲基赖氨酸 (CML)含量 ,放射免疫方法检测ET 1的生成 ,RT PCR的方法检测ET 1mRNA的表达 ,凝胶迁移率改变实验 (EMSA)检测BAECs核转录因子κB(NF κB)的DNA结合活性。结果 :糖尿病患者红细胞比正常人含有更多的CML修饰蛋白 ,HbA1c为 14 .3%的糖尿病患者的红细胞比正常人对BAECs的ET 1产生具有更高的诱导活性 ,其对NF κB的激活作用也明显增高 ;糖尿病患者的红细胞诱导BAECs的ET 1的产生与患者HbA1c水平相关 ,不仅能增加ET 1水平 ,还能增强ET 1mRNA的表达。结论 :AGE通过NF κB激活机制诱导ET 1的生成作用依赖于血糖水平的增高 ,这可能是糖尿病血管病变的重要发病机制。降低血糖水平 ,可以减少ET 1的产生 ,有效控制糖尿病血管并发症的发生、发展。
AIM: To investigate the effect of hyperglycemic glycation end products (AGE) on the induction of endothelin 1 (ET 1) production. Methods: Bovine aortic endothelial cells (BAECs) and diabetic patients were co-cultured with erythrocytes to induce ET 1 production. Western blot analysis of erythrocyte carboxymethyl lysine (CML) content, radioimmunoassay detection of ET 1 production, RT PCR method to detect ET 1mRNA expression, gel mobility shift assay (EMSA) BAECs nuclear transcription factor κB (NF κB) DNA binding activity. Results: Erythrocytes in diabetic patients contained more CML-modified protein than normal subjects, and HbA1c was found in 14.3% of diabetic patients. Compared with normal subjects, erythrocytes had higher induction activity on ET 1 production of BAECs and activation of NF κB Also significantly higher; diabetic erythrocyte-induced BAECs of ET 1 production in patients with HbA1c levels, not only can increase the ET 1 level, but also enhance the expression of ET 1mRNA. CONCLUSION: The effect of AGE on ET 1 production induced by NF κB activation depends on the increase of blood glucose level, which may be an important pathogenesis of diabetic vascular disease. Lower blood glucose levels, can reduce the production of ET 1, effectively control the occurrence and development of diabetic vascular complications.