炎症小体Nlrp3在高血压小鼠心肌纤维化中的作用  

Role of Nlrp3 inflammasome in ang II-induced hypertensive cardiac injury and fibrosis

作　　者：阿希[1,2] 李玉琳[1,2] 王绿娅[1,2] 吴依娜[1,2] 刘燕[1,2] 杜杰[1,2] 

机构地区：[1]首都医科大学附属北京安贞医院 [2]北京市心肺血管疾病研究所省部共建心血管重塑相关疾病教育部重点,100029

出　　处：《心肺血管病杂志》2015年第6期496-500,共5页Journal of Cardiovascular and Pulmonary Diseases

基　　金：国家自然科学基金(81230006);北京市自然科学基金(7132043;7142050;7142030);科研基地建设;心血管重大疾病防治协同创新中心(PXM2013_014226_000006)

摘　　要：目的:研究NOD样受体热蛋白结构域3(Nlrp3)炎症小体在高血压导致心脏纤维化重构中的作用与影响。方法:18只雄性C57BL/6J小鼠随机分为对照组(n=8)灌注0.9%氯化钠溶液,和血管紧张素(Ang II)组(n=10)灌注Ang II,采用鼠尾套管法测量小鼠血压。于灌注第7天后处死小鼠,收取心脏组织进行切片,采用免疫组织化学、H-E与Masson染色观测心脏炎症浸润与纤维化重构、使用q PCR检测炎症因子和nlrp3炎症小体表达与活化。结果:与对照组小鼠相比较,Ang II组小鼠在灌注后血压从第1天起持续升高,并持续到第7天。炎症因子白介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α以及诱导型一氧化氮合酶(i NOS)表达增加,巨噬细胞浸润增加,炎症小体表达增多,心脏中的间质胶原沉积增加,肌成纤维细胞标志α-SMA表达增加;与对照组相比,体外使用Ang II刺激巨噬细胞后,IL-1β表达升高,炎症小体nlrp3表达增加,给与P2X7受体(可以激活炎症小体nlrp3)抑制剂PPADS后,IL-1β与nlrp3转录水平表达降低。结论:高血压可能通过促进巨噬细胞内炎症小体nlrp3的表达,引起IL-1β的释放增多,促进心脏组织中巨噬细胞浸润,导致心脏组织损伤和纤维化加重。Objectlve：We aim at the role and expression of Nlrp3 inflammasome in cardiac inflamma- tion and damage after Ang II infusion. Methods： 18 male C57BL6/J mice were randomly divided into 2 groups ： Saline control （ n = 8 ） and Ang/I-infusion group （ 1 000ng·kg -1·min -1 ） （ n = 10 ）. Tail cuff system was performed to test blood pressure. Heart tissue was harvested in 7th day and prepared for forwarding test. H- E and Masson staining were used to detect inflammatory cell and fibrosis zone. Real-time PCR were used to de- tect expression of inflammasome. Results： Compared with Saline control, Ang Ⅱ-infusion group showed in- creased blood pressure （148 ±2） vs. （92 ±2）mmHg, 1 mmHg =0. 133 kPa, P 〈0.05） and abrogated cardiac infammation. Accumulated maerophage infiltration and enhanced expression of inflammasome were found in Ang II-induced heart tissue. In vitro, administrated with P2X7 inhibitor PPADS reduced inflammasome and IL- 1 β expression. Conclusion： Ang II could recruit macrophage infiltration in heart tissue during hypertension and activate inflammasome and increase IL-1β release, which may associated with Ang II-induced cardiac injury and fibrosis.

关 键 词：高血压 炎症小体 血管紧张素Ⅱ 巨噬细胞 炎症反应 

分 类 号：R54[医药卫生—心血管疾病]