缓激肽在血管紧张素（1～7）保护血管内皮细胞中的作用  

The Role of Bradykinin in Protective Effect of Angiotensin(1-7) on Endothelial Cell in Human Umbilical Vein Cells

作　　者：邹军[1] 任江华[1] 王虹[1] 冯丹[2] 徐江[2] 

机构地区：[1]武汉大学中南医院心内科 [2]武汉大学老年病研究所

出　　处：《中华高血压杂志》2007年第1期44-48,共5页Chinese Journal of Hypertension

摘　　要：目的观察缓激肽（BK）在血管紧张素（1～7）[Ang（1～7）]对血管紧张素Ⅱ（AngⅡ）致人脐静脉内皮细胞（HUVECs）损伤、凋亡中的影响及可能作用机制。方法体外培养HUVECs，随机分为6组：对照组，AngⅡ组，Ang（1～7）组，AngⅡ＋Ang（1～7）组，HOE-140组和AngⅡ＋Ang（1～7）＋HOE-140组。采用分光光度计测定培养的HUVECs乳酸脱氢酶（LDH）漏出，流式细胞仪技术检测细胞凋亡，硝酸还原酶法和放射免疫分析技术分别测定HUVECs上清液中一氧化氮（NO）和内皮素-1（ET-1）的含量，免疫组化法结合图像分析测定细胞间黏附分子-1（ICAM-1）的表达。结果（1）与对照组比较，AngⅡ（0．1μmol／L）孵育细胞24h后显著增加HUVECs的LDH漏出[（231．5±74．4vs76、6±19．4）U／L，P〈0．01]、ET-1分泌[（97．6±15．7vs48．8±9．3）pg／mL，P〈0．01]、ICAM-1表达[0．070±0．001vs0．041±0．003，P〈0．01]和HUVECs凋亡率[24．8％±0．6％vs1．4％±0．6％，P〈0．01]；Ang（1～7）（1μmol／L）明显抑制了AngⅡ的上述作用，同时还促进HUVECs NO的释放；（2）缓激肽B2受体拮抗剂HOE-140（1μmol／L）明显减弱Ang（1～7）对抗AngⅡ的作用（P〈0．01）；（3）单用Ang（1～7）、HOE-140对HUVECs无明显影响。结论Ang（1～7）能有效抑制AngⅡ引起的HUVECs的损伤和凋亡，其作用至少部分是通过BKB2受体介导的。Objective To investigate the potential role of bradykinin（BK） in the protective effects of angiotensin（1-7） fAng（ 1-7）] on human umbilical vein endothelial cells （HUVECs） injury and apoptosis induced by angiotensin Ⅱ （Ang Ⅱ ） in vitro culture. Methods Cultured HUVECs were randomly grouped as follows： control, Ang Ⅱ, Ang（1-7）, Ang Ⅱ＋Ang（1-7）, HOE-140, and Ang Ⅱ ＋Ang（1-7）＋HOE-140. Spectrophotometry and flow cytometry were used to evaluate lactate dehydrogenase （LDH） leakage and apoptosis percentage. Nitric oxide （NO） and endothelin-1（ET-1） levels were measured by colorimetry and radioimmunoassay. Expression of intercellular adhesion molecule-1（ICAM-1） in HUVEC membranes was determined by immunohistochemistry and image analysis. Results After incubating the HUVECs with 0.1 μmol/L Ang H for 24 hours, LDH leakage （231.5±74. 4 vs control：76. 6±19. 4 U/L, P〈0. 01）, ET-1 release （97. 6±15.7 vs control：48. 8±9. 3 pg/mL, P〈0.01 ）, expression of ICAM-1 （ 0. 070 ± 0. 001 vs control： 0. 041 ± 0. 003, P〈0.01 ）, and apoptosis percentage （24. 8%±0.6% vs control：l. 4%±0.6%, P〈0. 01） were significantly increased. These increases were inhibited hy cocultured with Ang（1-7 ） 1 μmol/L. BK subtype 2 receptor antagonist HOE-140 （1 μmol/L） attenuated the inhibiting effect of Ang（1-7） on the performance by Ang Ⅱ Neither Ang（1-7） nor HOE-140 alone had any effect on HUVECs. Conclusion Ang（1-7） was shown to have protective role on HUVECs via inhibition of Ang H induced injury and apoptosis. The protection effect may be partially mediated by bradykinin B2 receptor.

关 键 词：血管紧张素(1~7) 血管紧张素Ⅱ缓激肽 人脐静脉内皮细胞 凋亡 

分 类 号：R54[医药卫生—心血管疾病]