摘要
目的 探讨大黄素对血管紧张素Ⅱ(AngⅡ)诱导的主动脉瘤(abdominal aortic aneurysm, AAA)小鼠形成及MEK/ERK信号通路的影响。方法 通过皮下植入AngⅡ缓释泵1 000 ng/(min·kg)构建AAA小鼠模型。将小鼠随机共分为3组,即对照组、模型组和大黄素组;造模后的第1天开始,大黄素组每天给予20 mg/kg的量。对照组、模型组给予等体积的0.9%NaCl灌胃,连用药28 d。HE染色观察小鼠主动脉直径;试剂盒检测主动脉组织SOD、MDA、GPX相对含量;ELISA试剂盒检测心肌组织中IL-17、IL-1β、IL-6和TNF-α的含量;免疫组化检测AAA小鼠心肌组织MMP2、MMP9、iNOS和Arg-1。Western blotting检查AAA小鼠心肌组织MEK、p-MEK、ERK和p-ERK蛋白表达。结果 AngⅡ可明显诱导小鼠主动脉直径增大,上调主动脉组织MMP2、MMP9、iNOS、Arg-1、p-MEK、p-ERK蛋白表达、炎症因子IL-17、IL-1β、IL-6和TNF-α含量和MDA、GPX相对含量,降低组织中SOD含量;而大黄素可显著抑制MMP2、MMP9、iNOS、Arg-1、MEK、ERK、p-ERK蛋白表达和炎症因子IL-17、IL-1β、IL-6和TNF-α含量及MDA、GPX相对含量。结论 大黄素具有抗氧化和抑制炎性因子表达的作用,该保护作用可能与抑制MEK/ERK信号通路激活有关,从而抑制Ang II诱导小鼠的AAA形成。
Objective To investigate the effect of emodin on the formation of angiotensin Ⅱ(AngⅡ)-induced aortic aneurysm(AAA) in mice and the MEK/ERK signaling pathway.Methods An AAA mouse model was constructed by subcutaneously implanting an AngⅡ sustained-release pump 1000 ng/(min·kg).The mice were randomly divided into 3 groups, namely the blank group, the model group and the emodin group;The emodin group was given a daily dose of 20 mg/kg from the first day after modeling.The blank group and model group were given an equal volume of 0.9% NaCl intragastrically for 28 days.HE staining to observe the diameter of mouse aorta;Kit to detect the relative content of SOD, MDA, GPX in aortic tissue;ELISA kit to detect the content of IL-17, IL-1β, IL-6 and TNF-α in myocardial tissue;Immune group Chemical detection of MMP2, MMP9, iNOS and Arg-1 in myocardial tissues of AAA mice.Western blotting examined the expression of MEK,p-MEK, ERK and p-ERK protein in myocardial tissue of AAA mice.Results AngⅡ can obviously induce the diameter of mouse aorta to increase, and up-regulate MMP2, MMP9, iNOS, Arg-1, MEK, ERK, p-ERK protein expression, inflammatory factors IL-17, IL-1β, IL-6 and the relative content of TNF-α and MDA, GPX, reduce the SOD content in the tissue;While emodin can significantly inhibit MMP2, MMP9, iNOS, Arg-1, p-MEK, p-ERK protein expression and inflammatory factor IL-17, IL-1β, IL-6 and TNF-α content and relative content of MDA and GPX.Conclusion Emodin has the effect of antioxidant and inhibiting the expression of inflammatory factors.This protective effect may be related to inhibiting the activation of MEK/ERK signaling pathway, thereby inhibiting the formation of AAA in mice induced by AngⅡ.
作者
徐良
王晓东
李金旭
陈鹏
李佩佩
XU Liang;WANG Xiao-dong;LI Jin-xu;CHEN Peng;LI Pei-pei(Department of Cardiovascular Surgery,Nanyang the Second People's Hospital,Nanyang,Henan 473000,China)
出处
《医药论坛杂志》
2022年第19期10-14,18,共6页
Journal of Medical Forum
