摘要
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。
Objective:To study the role of glycemia in advanced glycated end products(AGE) mediated endothelin 1 (ET 1) induction.Methods:We grouped patients with type II diabetes according to the levels of HbA 1c:(HbA 1c<6%?HbA 1c 6.0 %～ 8.0 % and HbA 1c> 8.0 %).ET 1 was induced by incubation of BAECs with erythrocytes isolated from patients with different HbA 1c levels. ET 1 was determined by a radioimmunoassay. Western blot analysis was used to evaluate content of CML modified proteins in erythrocytes. RT PCR for ET 1 showed the expression of ET 1 mRNA. NF kB binding activity was monitored in EMSA.Results:Erythrocytes which derived from patients with poor glycemic control had more CML modified proteins and a stronger ET 1 inducing activity in cultured BAECs than erythrocytes derived from patients with good glycemic control. Their NF κB inducing activity was significant stronger than control. This study also indicates that CML modified proteins not only increase ET 1 concentration but also increase the expression of ET 1 mRNA in BAECs.Conclusion:AGE mediated ET 1 induction by NF kB activation is dependent on hyperglycemia. It may relate to the mechanism of vascular complication of diabetes. Control of hyperglycemia is the key issue to reduce ET 1 induction and prevention vascular complications of diabetes.
出处
《临床心血管病杂志》
CAS
CSCD
北大核心
2003年第3期142-144,共3页
Journal of Clinical Cardiology
