下丘脑室旁核内Toll样受体4轴对心肌梗死大鼠交感神经激活的影响  

Effects of Toll-like receptor 4 axis in the hypothalamic paraventricular nucleus on sympathetic activation in rats with myocardial infarction

作　　者：王康 殷洁 张学丽 闫素华[1] Wang Kang;Yin Jie;Zhang Xueli;Yan Suhua(Department of Cardiology,Shandong Qianfoshan Hospital,Cheeloo College of Medicine of Shandong University,Jinan 250012,Shandong Province,China)

机构地区：[1]山东省千佛山医院心内科,济南250012 [2]山东第一医科大学第一附属医院心内科 [3]北京清华长庚医院核医学科

出　　处：《中华老年心脑血管病杂志》2022年第7期755-759,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家自然科学基金(82070345)。

摘　　要：目的研究下丘脑室旁核内Toll样受体4(toll-like receptor 4,TLR4)/髓样分化因子88(MyD88)/NF-κB信号通路对心肌梗死模型SD大鼠交感神经过度激活导致室性心律失常的影响。方法选择SPF级雄性SD大鼠36只,分别于下丘脑室旁核定点微注射干扰腺病毒及其阴性对照腺病毒,每侧注射0.5μl,依次作为干扰病毒和对照病毒大鼠。4周后,结扎左冠状动脉前降支,建立急性心肌梗死(AMI)模型。将造模成功的24只大鼠依据处理不同随机分为对照组(对照病毒+假手术);病毒组(干扰病毒+假手术);模型组(对照病毒+AMI);干扰组(干扰病毒+AMI),每组6只。检测下丘脑室旁核内TLR4和离子化钙结合适配分子1(Iba-1)共定位情况,TLR4、MyD88、NF-κB、NF-κB抑制蛋白α(IκB-α)、细胞癌基因Fos(c-Fos)表达,血清和心肌去甲肾上腺素(NE)水平以及心律失常评分。结果与对照组比较,模型组TLR4、MyD88、NF-κB和Iba-1表达明显增加,IκB-α表达明显降低,血清和心肌组织NE水平明显增加(P<0.05,P<0.01);干扰组TLR4、MyD88、NF-κB和Iba-1表达明显增加,心肌组织NE水平明显增加(P<0.05,P<0.01)。与模型组比较,干扰组TLR4、MyD88、NF-κB和Iba-1表达明显降低,IκB-α表达明显增加,血清和心肌组织NE水平明显降低(P<0.05,P<0.01)。模型组c-Fos表达和心律失常评分较对照组明显增加(P<0.01)。干扰组c-Fos表达和心律失常评分较模型组明显降低[115.7±10.6 vs 164.0±25.2,(2.00±0.89)分vs(3.83±1.17)分,P<0.05]。结论下丘脑室旁核内TLR4轴可通过增加心肌梗死后交感神经的过度激活导致室性心律失常的发生。Objective To investigate the effects of Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/NF-κB signaling pathway on ventricular arrhythmias caused by sympathetic hyperactivation in SD rat model of myocardial infarction.Methods Thirty-six male SD rats of SPF class were selected and microinjected with interfering adenovirus or negative control adenovirus in the hypothalamic paraventricular nucleus(PVN),0.5μl on each side,and in turn served as interfering virus and control virus rats.In 4 weeks later,the left anterior descending coronary artery was ligated to establish a model of acute myocardial infarction(AMI).Then the 24 rats successfully modeled were divided into control group(control virus+sham operation),virus group(interfering virus+sham operation),model group(control virus+AMI),and interference group(interfering virus+AMI)according to different treatments they recieved,with 6 rats in each group.The co-localization of TLR4 and Iba1 in the hypothalamic PVN,as well as the expression of TLR4,MyD88,NF-κB,IκB-α,c-Fos,serum and myocardial NE levels,and arrhythmia score were measured.Results When compared with the control group,the expression levels of TLR4,MyD88,NF-κB and Iba1 were obviously elevated and that of IκB-αwas notably decreased significantly decreased,while serum and myocardial NE levels were remarkably increased in the model group(P<0.05,P<0.01);the expression levels of TLR4,MyD88,NF-κB and Iba1 were statistically increased and the NE level in myocardial tissue was reduced in the interference group(P<0.05,P<0.01).The interference group had significantly decreased levels of TLR4,MyD88,NF-κB and Iba1,upregulated IκB-αexpression,and reduced serum and myocardial NE levels than the model group(P<0.05,P<0.01).The c-Fos expression and arrhythmia score were significantly increased in the model group than the control group(P<0.01),and the expression and the score were notably lower in the interference group than the model group(115.7±10.6 vs 164.0±25.2,2.00±0.89 vs 3.83±1.17,P<

关 键 词：下丘脑室旁核 TOLL样受体4 心肌梗死 髓样分化因子88 NF-ΚB 

分 类 号：R542.22[医药卫生—心血管疾病]