低氧诱导因子-1α减轻七氟烷处理小鼠心肌缺血再灌注损伤中的研究  被引量:2

Effect of hypoxia inducible factor-1 on post-treatment of sevoflurane in alleviating myocardial ischemia-reperfusion injury in mice

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作  者:徐聪杰 景晓刚[2] XU Congjie;JING Xiaogang(Department of Anesthesiology of General Hospital of Pingmei Shenma Medical Group,Pingdingshan 467002,China)

机构地区:[1]平煤神马医疗集团总医院麻醉科,467002 [2]郑州大学第一附属医院呼吸科

出  处:《心肺血管病杂志》2019年第5期544-549,共6页Journal of Cardiovascular and Pulmonary Diseases

基  金:河南省高等学校重点科研项目计划(19A320032)

摘  要:目的:探究HIF-1α对于使用七氟烷后处理的小鼠减轻其心肌缺血/再灌注损伤的相关机制。方法:将8周龄小鼠随机分为四组分别进行假手术,心肌缺血/再灌注,HIF-1α稳定剂+心肌缺血/再灌注,HIF-1α抑制剂+心肌缺血/再灌注。对心肌缺血/再灌注模型采取经典的结扎冠状动脉左前降支,之后对小鼠进行七氟烷后处理。分别检测四组大鼠的心肌组织中HIF-1α,NF-κB,TLR4,SOD的蛋白表达水平以及相关mRNA水平,凋亡相关蛋白Bax,BCL2的表达水平,心肌组织MPO活性等。结果:在进行处理之前,四组小鼠的AAR/LV以及An/AAR差异无统计学意义(P>0.05);经过处理后,I/R组小鼠的AAR/LV以及An/AAR均显著高于对照组(P<0.001),DMOG+I/R组相比I/R组,AAR/LV以及An/AAR均发生了显著降低(P<0.001),YC-1+I/R组相比I/R组,AAR/LV以及An/AAR又均发生了显著升高(P<0.01);当小鼠发生心肌缺血/再灌注时,小鼠体内的HIF-1α蛋白水平显著下调,炎症因子NF-κB和TLR4显著上升,抗氧化蛋白SOD显著下降,促凋亡蛋白Bax显著升高,抗凋亡蛋白BCL2水平显著下降;而当在此基础上加入HIF-1α增强剂DMOG时,可以使炎症因子NF-κB和TLR4显著下调,抗氧化蛋白SOD显著上升,促凋亡蛋白Bax显著下降,抗凋亡蛋白BCL2水平显著升高,加入HIF-1α抑制剂YC-1现象相反;I/R组小鼠的NF-κB和TLR4水平显著升高(t=4.687,5.124,P<0.05),DMOG+I/R组相比I/R组,其NF-κB和TLR4水平发生显著下降(t=4.112,4.197,P<0.05),YC-1+I/R组相比I/R组,其NF-κB和TLR4水平发生显著回升(t=2.335,2.138,P<0.05);经过处理之后,对照组小鼠的MPO活性为(0.28±0.54),I/R组小鼠的为(1.45±0.31),显著升高(t=3.875,P<0.05),DMOG+I/R组的为(0.88±0.23),相比I/R组发生了显著降低(t=3.224,P<0.05);而YC-1+I/R组的为(1.98±0.39),相比I/R组发生了显著回升(t=3.015,P<0.05)。结论:HIF-1α可有效减轻大鼠在心肌损伤/再灌注所致的炎性损伤并避免心肌细胞凋亡,对心肌细胞起到良好的保�Objective:To explore the mechanism by which hypoxia inducible factor-1(HIF-1α)attenuates myocardial ischemia/reperfusion injury in mice treated with sevoflurane.Methods:Eight-week-old mice were randomly divided into 4 groups for sham operation,myocardial ischemia/reperfusion,HIF-1αstabilizer+myocardial ischemia/reperfusion,HIF-1αinhibitor+myocardial ischemia/reperfusion.Classical ligation of the left anterior descending coronary artery was performed on the myocardial ischemia/reperfusion model,after which the mice were treated with sevoflurane.The protein expression levels of HIF-1α,NF-κB,TLR4,SOD and related mRNA levels,expression levels of apoptosis-related proteins Bax and BCL2,and MPO activity of myocardial tissue were detected in the myocardial tissues of the four groups.Results:There were no significant difference in AAR/LV and An/AAR between the four groups before treatment(P>0.05).After treatment,the AAR/LV and An/AAR of the I/R group were significantly higher than the control group(P<0.001),the DMOG+I/R group showed a significant decrease(P<0.001)compared with the I/R group in AAR/LV and An/AAR,and in the YC-1+I/R group,AAR/LV and An/AAR both increased significantly than that in the I/R group(P<0.01);When myocardial ischemia/reperfusion occurred in mice,the level of HIF-1αprotein in mice was significantly down-regulated,the inflammatory factors NF-κB and TLR4 increased significantly,the antioxidant protein SOD decreased significantly,and the pro-apoptotic protein Bax increased significantly.The anti-apoptotic protein BCL2 level decreased significantly.When the HIF-1αenhancer DMOG was added,the inflammatory factors NF-κB and TLR4 were significantly down-regulated,the antioxidant protein SOD was significantly increased,and the pro-apoptotic protein Bax was significantly decreased.The level of anti-apoptotic protein BCL2 was significantly increased.The phenomenon of addition of HIF-1αinhibitor YC-1 was reversed;the levels of NF-κB and TLR4 in I/R mice were significantly increased(t=4.687,5.124,P<

关 键 词:低氧诱导因子-1Α 心肌损伤/再灌注 炎症 凋亡 

分 类 号:R54[医药卫生—心血管疾病]

 

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