NLRP3炎症小体介导血管紧张素Ⅱ诱导的人脐静脉血管内皮细胞炎症因子IL-1β的表达  

NLRP3 inflammasome mediates angiotension Ⅱ-induced expression of inflammatory factor interleukin-1β in human umbilical vein endothelial cells

作　　者：杨仁强[1] 黄玲[1] 马晓欣[2] 金思一 王丹[2] 李旭[3] 

机构地区：[1]南方医科大学南方医院急诊科,广东广州510515 [2]南方医科大学南方医院消化科,广东广州510515 [3]南方医科大学南方医院感染内科,广东广州510515

出　　处：《南方医科大学学报》2016年第6期790-795,共6页Journal of Southern Medical University

基　　金：国家自然科学基金(30770974)~~

摘　　要：目的研究血管紧张素Ⅱ(AngⅡ)对人脐静脉血管内皮细胞(HUVECs)NLPR3炎症小体激活与炎症因子白介素-1β(IL-1β)表达的影响。方法体外培养HUVECs,用AngⅡ的不同浓度和刺激时间刺激HUVECs,找到最适合的AngⅡ刺激浓度与时间。AngⅡ刺激HUVECs前,预用AngⅡ受体阻断剂氯沙坦阻断AngⅡ作用;NAD(P)H抑制剂DPI或H2O2清除剂CAT降低胞内活性氧(ROS)含量;用caspase-1抑制剂YVAD阻断caspase-1作用;用NLRP3 si RNA沉默胞内NLRP3表达。运用蛋白印迹法(western blot)分别检测细胞内NOX4、NLRP3、caspase-1以及IL-1β含量。结果(1)HUVECs在浓度10-9M AngⅡ刺激12 h后,胞内NOX4、NLRP3、caspase-1以及IL-1β的蛋白表达显著增加;(2)氯沙坦、DPI、CAT、YVAD和NLRP3 si RNA都可减轻AngⅡ诱导的上述反应。结论 AngⅡ通过促进HUVECs活性氧生成,激活NLRP3炎症小体,促进胞内炎症介质IL-1βP17活性片段生成增加,诱导血管炎症的发生。Objective To investigate the effect of angiotension II（Ang II） on the activation of NLRP3 inflammasome and the expression of interleukin-1β（IL-1β） in human umbilical vein endothelial cells（HUVECs）. Methods HUVECs cultured in vitro were treated with different concentrations of Ang II for varying lengths of time to determine the optimal concentration and time for Ang II exposure. To test the impact of different agents on the effect of Ang II exposure, HUVECs were pretreated with Ang II receptor blocker losartan, NAD（P）H inhibitor DPI and H2O2 scavenger CAT, caspase 1 inhibitor YVAD, or NLRP3 si RNA for silencing NLRP3, and the protein levels of NOX4, NLRP3, caspase- 1 and IL- 1β in HUVECs were analyzed by Western blotting. Results Ang II treatment at the optimal concentration（10- 9mol/L） for 12 h significantly increased the protein levels of NOX4, NLRP3, caspase1 and IL-1β in HUVECs. Pretreatment with losartan, DPI, CAT, YVAD, or NLRP3 si RNA all attenuated the effects of Ang II on the cells. Conclusion Ang II can induce vascular inflammation by promoting the production of reactive oxygen species and activating NLRP3 inflammasome to increase the protein expression of IL-1β in HUVECs.

关 键 词：血管紧张素Ⅱ 脐静脉内皮细胞 活性氧 NLRP3炎症小体 白介素-1Β 

分 类 号：R54[医药卫生—心血管疾病]