苯肾上腺素对心肌纤维化的调节和对白细胞介素-1、白细胞介素-6及肿瘤坏死因子-α的影响

王硕，庞晓，曹慧



苯肾上腺素对心肌纤维化的调节和对白细胞介素-1、白细胞介素-6及肿瘤坏死因子-α的影响

王硕，庞晓，曹慧

摘要

关键词肾上腺素α1受体激动剂；心肌纤维化；白细胞介素-1；白细胞介素-6；肿瘤坏死因子-α

作者单位：832002 新疆维吾尔自治区石河子市，石河子大学医学院第一附属医院 心内科

Impacts of Phenylephrine on Myocardial Fibrosis Regulation and Interleukin-1,Interleukin-6,Tumor Necrosis Factor-α Expressions in Experimental Mice

WANG Shuo,PANG Xiao,CAO Hui.
Department of Cardiology,First Affiliated Hospital of Shihezi University Medical College,Shihezi(832002),Xinjiang,China
Corresponding Author:PANG Xiao,Email:px0993@163.com

Abstract

Objective:To explicit phenylephrine(PE),α1-adrenergic receptor(α1-AR)on myocardial fibrosis regulation and interleukin-1(IL-1),IL-6,tumor necrosis factor-α(TNF-α)expressions in pressure overloaded mice.

Methods:A total of 49 KM mice were randomly divided into 3 groups:Blank control group,n=7,Sham operation group,n=7,Transverse abdominal aortic constriction(TAC)group,n=35,and 8 weeks later,the mice in TAC group were further divided into 5 sub-groups as TAC control,TAC+PE,TAC+Praz,TAC+Prop,TAC+Carv sub-groups,n=5 in each sub-group,and the animals were respectively treated for 3 weeks.Left ventricular collagen volume fraction(CVE),hydroxyproline content and IL-1,IL-6,TNF-α expressions were examined respectively.

Results:By 8 weeks treatment,compared with Blank control group,TAC group had obvious myocardial fibrosis,increased hydroxyproline content and IL-1,IL-6,TNF-α expressions,P<0.001.Compared with TAC control sub-group,TAC+PE,AC+Prop,TAC+Carv sub-groups showed decreased CVF,hydroxyproline content and IL-1,IL-6,TNF-α expressions,P<0.001,while the above changes were not obvious in TAC+Praz sub-group,P>0.05;CVE and hydroxyproline content were similar between TAC+PE and TAC+Prop sub-groups,while the expressions of IL-1,IL-6 and TNF-α were obviously decreased in TAC+Prop sub-group,P<0.05.Conclusion:PE may improve myocardial fibrosis and IL-1,IL-6,TNF-α expressions by activating α1-AR in pressure overloaded mice,α1-AR might be a defending factor for myocardial fibrosis.

Key words Adrenergic alpha-1 receptor agonists;Myocardial fibrosis;Interleukin-1;Interleukin-6;Tumor necrosis factor-α

(Chinese Circulation Journal,2016,31:289.)

心肌纤维化是指在正常的心脏组织结构中胶原纤维过量积聚、胶原浓度显著升高或胶原成分发生变化，是胶原合成代谢和分解代谢失衡的结果。这种病理表现存在于多种心血管疾病，与心功能障碍、心律失常甚至心原性猝死密切相关。交感神经系统活性增加在心血管病的发生、发展中有着重要的作用[1]。基础实验与临床研究已证实，β肾上腺素能受体（β-AR）阻滞剂能够延缓心血管病进展，降低心力衰竭的发病率和死亡率[2]，但是，与β-AR在心脏中的作用已受到广泛关注不同，有关α1肾上腺素能受体（α1-AR）的研究报道较少。

炎症因子在多种疾病所致的心肌纤维化进程中起着重要作用。各种致病因素导致心肌组织炎性细胞浸润、炎症因子水平异常增高，刺激心脏胶原纤维合成增多，最终导致心肌纤维化。急性心肌梗死后的梗死区和非梗死区都存在炎性细胞浸润和心肌纤维化，且炎症因子的水平与纤维化的程度密切相关。炎症因子在心肌纤维化过程中形成了一个复杂的调节网络，在炎症因子的刺激下，发生纤维化的心肌组织进一步分泌炎症因子，从而导致恶性循环。……