首页|NADPH氧化酶抑制剂Apocynin预防脂多糖心肌纤维化的研究

NADPH氧化酶抑制剂Apocynin预防脂多糖心肌纤维化的研究

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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Col Ⅰ al、ColⅢal、MMP2、MMP9 mRNA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Col Ⅰ a1、ColⅢa1、MMP2、MMP9 mRNA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gp91phox和p67phox过表达有关.
NADPH oxidase inhibitor-apocynin in preventing cardiac fibrosis in mice exposed to subclinical lipopolysaccharide
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 C57BL/6J mice were divided randomly into 4 groups:control group,apocynin group,LPS group and LPS + apocynin group.LPS was injected intraperitoneally once a week for 4 weeks to mimic cardiac fibrosis in LPS group and LPS + apocynin group.Apocynin was given in apocynin group and LPS + apocynin group,once a week for 4 weeks.Collagen fraction area of the left ventricle was measured with picrosirius red staining.The cardiac expression of fibrosis-related genes was measured by RT-PCR.The subunits gp91 phox and p67phox of NADPH oxidase were analyzed by Western blot,ROS production was determined by DHE staining.Results The cardiac fibrosis of mice occurred after 4 weeks.Compared with control group,the interstitial diffuse fibrous tissue in myocardium,the collagen volume fraction,the mRNA expression of LPS-induced activation of fibrosis-related genes Col Ⅰ a 1,Col Ⅲ a1,MMP2 and MMP9,the expression gp91 phox and p67phox and ROS production in LPS group were increased.Compared with 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 gp91phox and p67phox.

LipopolysaccharideApocyninNADPH oxidaseFibrosis

黄礼兵、邹蓉、朱明慧、周玉弟、郑曼

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南京中医药大学附属医院麻醉科,南京210029

脂多糖 夹竹桃麻素 NADPH氧化酶 纤维化

2017

实用药物与临床
辽宁省药学会,中国医科大学附属盛京医院

实用药物与临床

CSTPCD
影响因子:1.633
ISSN:1673-0070
年,卷(期):2017.20(10)
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