首页|期刊导航|中华医学杂志（英文版）|Probucol attenuates atrial autonomic remodeling in a canine model of atrial fibrillation produced by prolonged atrial pacing
中华医学杂志（英文版）2009，Vol.122Issue(1)：74-82,9.DOI:10.3760/cma.j.issn.0366-6999.2009.01.014
Probucol attenuates atrial autonomic remodeling in a canine model of atrial fibrillation produced by prolonged atrial pacing
Probucol attenuates atrial autonomic remodeling in a canine model of atrial fibrillation produced by prolonged atrial pacing
摘要
Abstract
Background We hypothesize that increased atrial oxidative stress and inflammation may play an important role in atrial nerve sprouting and heterogeneous sympathetic hyperinnervation during atrial fibrillation (AF). To test the hypothesis, we examined whether the antioxidant and anti-inflammatory treatment with probucol attenuates atrial autonomic remodeling in a canine model of AF produced by prolonged rapid right atrial pacing. Methods Twenty-one dogs were divided into a sham-operated group, a control group and a probucol group. Dogs in the control group and probucol group underwent right atrial pacing at 400 beats per minute for 6 weeks, and those in the probucol group received probucol 1 week before rapid atrial pacing until pacing stopped. After 6-week rapid atrial pacing, general properties including left atrial structure and function, atrial hemodynamics and the inducibility and duration of AF were measured in all the groups. Atrial oxidative stress markers and serum C-reactive protein (CRP) concentration were estimated. The degree of nerve sprouting and sympathetic innervation at the right atrial anterior wall (RAAW) and the left atrial anterior wall (LAAW) were quantified by immunohistochemistry, atdal norepinephrine contents were also detected. Atrial beta-nerve growth factor (beta-NGF) mRNA and protein expression at the RAAW and LAAW were assessed by real-time quantitative RT-PCR and Western blotting respectively. Results Atrial tachypacing induced significant nerve sprouting and heterogeneous sympathetic hyperinnervation, and the magnitude of nerve sprouting and hyperinnervation was higher in the RAAW than in the LAAW. Atrial beta-NGF mRNA and protein levels were significantly increased at the RAAW and LAAW, and the upregulation of beta-NGF expression was greater at the RAAW than at the LAAW in the control group. The beta-NGF protein level was positively correlated with the density of sympathetic nerves in all groups. Probucol decreased the increase of CRP concentration and attenuated atrial oxidative stress caused by atrial tachypacing. In addition, probucol could effectively inhibit atrial beta-NGF upregulation, significantly attenuate atrial nerve sprouting and heterogeneous sympathetic hyperinnervation, and dramatically reduce the inducibility and duration of AF. Conclusions The atrial over-expression of beta-NGF possibly caused by increased oxidative stress and inflammation may be the main mechanism underlying atrial autonomic remodeling during AF. Probucol attenuates atrial autonomic remodeling possibly by its antioxidant and anti-inflammatory actions.关键词
atrial fibrillation/nerve growth factor/autonomic nervous system/oxidative stress/inflammationKey words
atrial fibrillation/nerve growth factor/autonomic nervous system/oxidative stress/inflammation分类
医药卫生引用本文复制引用
GONG Yong-tai,LI Wei-min,LI Yue,YANG Shu-sen,SHENG Li,YANG Ning,SHAN Hong-bo,XUE Hong-jie,LIU Wei,YANG Bao-feng,DONG De-li,LI Bao-xin..Probucol attenuates atrial autonomic remodeling in a canine model of atrial fibrillation produced by prolonged atrial pacing[J].中华医学杂志（英文版）,2009,122(1):74-82,9.基金项目
This study was partially supported by the National Basic Research Program of China (973 Program: No. 2007CB512000, 2007CB512006), and was fully supported by the Key Science and Technology Program of Heilongjiang Province (No. GB07C32401), the Program for New Century Excellent Talents in University from the Department of Education of Heilongjiang Province (No. 1152-NCET-011), the Scientific Research Foundation of the First Clinical Hospital of Harbin Medical University and the Doctorate Foundation of Harbin Medical University (No. HCXB2007016). This study was also funded by the Harbin Science and Technology Department (No. 2005AA9CS 116-1) （973 Program: No. 2007CB512000, 2007CB512006）
