NADPH氧化酶抑制剂Apocynin预防脂多糖心肌纤维化的研究  

NADPH oxidase inhibitor-apocynin in preventing cardiac fibrosis in mice exposed to subclinical lipopolysaccharide

作　　者：黄礼兵[1] 邹蓉[1] 朱明慧[1] 周玉弟[1] 郑曼[1] HUANG Li-bing ZOU Rong ZHU Ming-hui ZHOU Yu-di ZHENG Man(Department of Anesthesiology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China)

机构地区：[1]南京中医药大学附属医院麻醉科,南京210029

出　　处：《实用药物与临床》2017年第10期1119-1122,共4页Practical Pharmacy and Clinical Remedies

摘　　要：目的探讨NADPH氧化酶抑制剂Apocynin对脂多糖(Lipopolysaccharide,LPS)心肌纤维化的预防作用。方法 40只小鼠随机分成4组:对照组(CON)、Apocynin组、LPS组和LPS+Apocynin组,每组10只。LPS组和LPS+Apocynin组给予LPS 10 mg/kg,每周1次,连续4周;Apocynin组和LPS+Apocynin组给予Apocynin 10 mg/kg,1次/d,连续4周。采用天狼星红染色评估心肌纤维化程度,RT-PCR检测ColⅠa1、ColⅢa1、MMP2、MMP9 m RNA的表达,Western blot检测心肌gp91^(phox) 和p67^(phox)的表达,DHE检测心肌活性氧生成。结果小鼠LPS注射4周后出现心肌纤维化。与对照组比较,LPS组心肌间质内弥漫性纤维组织显著增多,胶原容积分数增加,心肌组织中胶原相关因子ColⅠa1、ColⅢa1、MMP2、MMP9 m RNA表达明显增加,心肌gp91^(phox) 和p67^(phox)的表达增加,ROS生成增加(P<0.05)。与LPS组比较,Apocynin干预可抑制上述指标的增加(P<0.05)。结论 Apocynin能预防LPS诱导小鼠心肌纤维化,其效应可能与抑制心肌gp91^(phox) 和p67^(phox)过表达有关。Objective To investigate the preventive effects of apocynin,an NADPH oxidase inhibitor,on cardiac fibrosis in mice exposed to subclinical lipopolysaccharide. Methods Totally 40 male C57 BL/6 J mice w ere divided randomly into 4 groups： control group,apocynin group,LPS group and LPS ＋ apocynin group. LPS w as injected intraperitoneally once a w eek for 4 w eeks to mimic cardiac fibrosis in LPS group and LPS ＋ apocynin group. Apocynin w as given in apocynin group and LPS ＋ apocynin group,once a w eek for 4 w eeks. Collagen fraction area of the left ventricle w as measured w ith picrosirius red staining. The cardiac expression of fibrosis-related genes w as measured by RT-PCR. The subunits gp91^phox and p67^phoxof NADPH oxidase w ere analyzed by Western blot,ROS production w as determined by DHE staining. Results The cardiac fibrosis of mice occurred after 4 w eeks. Compared w ith control group,the interstitial diffuse fibrous tissue in myocardium,the collagen volume fraction,the m RNA expression of LPS-induced activation of fibrosis-related genes ColⅠa1,ColⅢa1,M M P2 and M M P9,the expression gp91^phox and p67^phoxand ROS production in LPS group w ere increased. Compared w ith LPS group,apocynin decreased the above indexes significantly（ P〈0. 05）. Conclusion Apocynin can protect against the cardiac fibrosis in mice exposed to subclinical LPS by inhibiting the over-expression of myocardial gp91^phox and p67^phox.

关 键 词：脂多糖 夹竹桃麻素 NADPH氧化酶 纤维化 

分 类 号：R965[医药卫生—药理学]