血管紧张素Ⅱ对人胰岛B细胞分泌功能的影响及氯沙坦的保护作用  

Losartan improves human islet β-cell function damaged by angiotensin Ⅱ

作　　者：刘敏[1] 蔡德鸿[1] 张桦[1] 鲁辛[1] 孙嘉[1] 张振[1] 李明[1] 

机构地区：[1]南方医科大学附属珠江医院内分泌科,广东广州510282

出　　处：《中国实用内科杂志》2007年第23期1836-1838,共3页Chinese Journal of Practical Internal Medicine

基　　金：国家自然科学基金(30470829);广东省科技计划项目(B30201)

摘　　要：目的动态监测血管紧张素Ⅱ(AngⅡ)对分离纯化人胰岛B细胞分泌功能的影响,探讨AngⅡ1型受体(AT1受体)阻滞剂氯沙坦(Losartan)预处理对AngⅡ致人胰岛B细胞功能损伤的保护作用及相关机制。方法2006年3月至10月,对南方医科大学附属珠江医院器官移植中心提供的成人尸体供胰进行人胰岛细胞的培养,并以AngⅡ及氯沙坦作用于分离纯化的人胰岛细胞,检测胰岛B细胞内游离Ca2+及钙调素(CaM)的波动情况;以胰岛灌流实验,绘制胰岛素动态分泌曲线。结果AngⅡ对胰岛B细胞分泌功能的影响呈先升后降双向性,AngⅡ使胰岛B细胞内游离Ca2+浓度升高,此作用可被氯沙坦所逆转。AngⅡ对细胞内CaM无明显影响。结论AngⅡ通过与胰岛B细胞表面AT1受体结合,使细胞内游离Ca2+波动,导致胰岛B细胞功能损伤,氯沙坦预处理通过抑制钙超载,保护AngⅡ致人胰岛B细胞功能损伤。Objective This study aimed to investigate the effects of angiotensin Ⅱ and Ⅰ,osartan pretreatment on regulating insulin secretion in hmuan islet β cells. Methods We measured changes in intracellular calcium by confocal laser scanning microscopy using Flou3-AM-loaded human islet cells, RT-PCR was used to measure changes in intracellular CaM. Dynamic insulin secretory responses were determined by chemiluminescence following perfusion of human islets. Results Exposure of the isolated islets to augiotensin Ⅱ reduced glucose-stimulated insulin release coupled with intracellular calcium ascending in first phase and descending in second phase. Intracellular CaM concentration could not be affected by angiotensin Ⅱ. Conclusion The change of free Ca^2 ＋ is induced by the comhination of Ang Ⅱ with ATI receptors of islet B cells,which resuhs in the damage to islel B cells. Losartan pretreatment protects the islet B-cell function by inhibiting calcium overload.

关 键 词：血管紧张素Ⅱ 人胰岛B细胞 CA^2+ 钙调素 

分 类 号：R5[医药卫生—内科学]