HIF-1α抗心肌缺血再灌注炎性损伤的作用  

Hypoxia-inducible factor-1α attenuates myocardial inflammatory injury induced by ischemia and reperfusion in rats

作　　者：王文香[1] 张妞妞 曾先燕 李廷瑞 吉晔楠 贺忠梅[1] WANG Wen-xiang;ZHANG Niu-niu;ZENG Xian-yan;LI Ting-rui;JI Ye-nan;HEZhong-mei(Department of Physiology,School of Basic Medical Sciences,Shanxi Medical University,Taiyuan 030001,China;Department of Materials and Chemical Engineering,Suzhou University,Jiangsu 215123,China)

机构地区：[1]山西医科大学基础医学院生理学系,细胞生理学山西省重点实验室,山西太原030001 [2]苏州大学材料与化学化工学部,江苏苏州215123

出　　处：《中国病理生理杂志》2018年第7期1201-1205,共5页Chinese Journal of Pathophysiology

基　　金：山西省自然科学基金资助项目(No.201601D011115、No.2012011040-7); 山西医科大学科技创新基金资助项目(No.01201501)

摘　　要：目的:本文旨在通过稳定低氧诱导因子1α(HIF-1α)表达,探讨其在大鼠心肌缺血再灌注(I/R)所致炎性损伤中的作用及可能的机制。方法:60只清洁级雄性Wistar大鼠随机分为4组:假手术(sham)组、I/R组、HIF-1α稳定剂二甲基乙二酰甘氨酸(DMOG)+I/R组和HIF-1α抑制剂YC-1+I/R组。各组分别予相应处理后,用Western blot法检测心肌组织的Toll样受体4(TLR4)和核因子κB(NF-κB)的蛋白表达;real-time PCR检测白细胞介素1β(IL-1β)、IL-6、肿瘤坏死因子α(TNF-α)、TLR4和NF-κB的mRNA水平;并利用试剂盒检测心肌组织的髓过氧化物酶(MPO)活性;HE染色观察炎性细胞浸润情况。结果:HIF-1α可明显降低心肌组织中炎性细胞的浸润、MPO活性及炎症因子IL-1β、IL-6和TNF-α的mRNA水平,同时降低TLR4和NF-κB的mRNA及蛋白水平(P<0.05)。结论:HIF-1α可减轻心肌I/R引起的炎性损伤,其机制可能与抑制TLR4/NF-κB信号通路激活有关。AIM： To investigate the role of hypoxia-inducible factor-1α（ HIF-1α） stable expression in myocardial inflammatory injury induced by ischemia and reperfusion（ I/R） in rats. METHODS： Male Wistar rats were randomly divided into 4 groups： sham operation（ sham） group, I/R group, HIF-1α stabilizer dimethyloxalyl glycine（ DMOG） ＋ I/R group and HIF-1α inhibitor YC-1 ＋ I/R group. The protein expression of myocardial Toll-like receptor 4（ TLR4） and nuclear factor-κB（ NF-κB） was determined by Western blot. The mRNA levels of interleukin（ IL）-1β,tumor necrosis factor-α（ TNF-α）,IL-6,TLR4 and NF-κB were detected by real-time PCR. The myeloperoxidase（ MPO）activity in the myocardial tissues was measured. HE staining was used to observe the infiltration of inflammatory cells. RESULTS： HIF-1α decreased the infiltration of inflammatory cells,the MPO activity,and the mRNA levels of inflammatory factors IL-1β,IL-6 and TNF-α in the myocardial tissues. HIF-1α also reduced the expression of TLR4 and NF-κB at mRNA and protein levels（ P〈0. 05）. CONCLUSION： The stable expression of HIF-1α has an anti-inflammatory effect on the myocardial tissues after I/R injury in rats. The mechanism may be related to the inhibition of TLR4/NF-κB signaling pathway.

关 键 词：低氧诱导因子1Α 心肌缺血再灌注损伤 炎症 TLR4/NF-κB信号通路 

分 类 号：R542.2[医药卫生—心血管疾病] R363[医药卫生—内科学]