芪丹通脉片对ApoE-/-小鼠动脉粥样硬化易损斑块及NLRP3炎症小体的影响  

Effects of Qidan Tongmai tablets on atherosclerotic vulnerable plaque and NLRP3 inflammasome in ApoE-/-mice

作　　者：杨槟钰 王南丁 马振 李哲[3] 王李雯[3] 张莎 陈晋玉 全依晨 YANG Binyu;WANG Nanding;MA Zhen;LI Zhe;WANG Liwen;ZHANG Sha;CHEN Jinyu;QUAN Yichen(Shaanxi University of Traditional Chinese Medicine,Xianyang 712046,Shaanxi,China;Xi’an Hospital of Traditional Chinese Medicine,Xi'an 710021,Shaanxi,China;The First Clinical Medical College of Shaanxi University of Traditional Chinese Medicine,Xianyang 712046,Shaanxi,China;School of Basic Medicine,Shaanxi University of Traditional Chinese Medicine,Xianyang 712046,Shaanxi,China)

机构地区：[1]陕西中医药大学,陕西咸阳712046 [2]西安市中医医院,陕西西安710021 [3]陕西中医药大学第一临床医学院,陕西咸阳712046 [4]陕西中医药大学基础医学院,陕西咸阳712046

出　　处：《现代中西医结合杂志》2022年第17期2354-2359,2391,共7页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：陕西省自然科学基础研究计划项目(2020JQ-966);西安市科协青年人才托举计划项目(095920201330);陕西中医药大学学科创新团队(2019-YS01)。

摘　　要：目的探讨芪丹通脉片是否可以通过抑制NLRP3炎症小体激活干预ApoE-/-小鼠动脉粥样硬化易损斑块的形成。方法将小鼠随机分为对照组、不稳定斑块组、益气组、活血组和复方组,每组12只。实验过程中对照组小鼠给予普通饲料饲养,其余组均给予高脂饲料喂养;同时益气组灌胃黄芪浸膏干粉溶剂(0.52 g生药/kg),活血组灌胃丹参浸膏干粉溶剂(1.31 g生药/kg),复方组灌胃芪丹通脉片浸膏干粉溶剂(2 g生药/kg),对照组和不稳定斑块组灌胃等体积生理盐水,均1次/d。连续灌胃14 d后,对各组小鼠进行右侧颈动脉外置管术,术后继续原来干预12周。干预结束后,麻醉小鼠,摘其眼球取血,ELISA法检测外周血中白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)水平;分离颈总动脉,采用HE染色及CD68、α-actin免疫荧光染色观察小鼠颈动脉斑块稳定情况;RT-PCR法检测斑块组织中NLRP3、Caspase-1 mRNA表达情况,Western blot法检测斑块组织中NLRP3、Caspase-1蛋白表达情况。结果不稳定斑块组血清IL-1β及IL-18水平均明显高于对照组(P均<0.05);益气组、活血组、复方组血清IL-1β及IL-18水平均明显低于不稳定斑块组(P均<0.05),且复方组均明显低于益气组、活血组(P均<0.05),益气组与活血组比较差异均无统计学意义(P均>0.05)。HE染色显示对照组小鼠颈动脉壁光滑,无斑块;不稳定斑块组小鼠颈动脉管腔内存在大量斑块沉积,斑块内部脂质池较大,斑块结构较不稳定;与不稳定斑块组比较,益气组、活血组、复方组小鼠斑块内部脂质池缩小,斑块的结构趋于稳定,其中复方组斑块结构最稳定。CD68、α-actin免疫荧光染色显示:对照组平滑肌细胞较多,巨噬细胞非常少;不稳定斑块组巨噬细胞明显增多,平滑肌细胞显著减少;益气组、活血组、复方组巨噬细胞较不稳定斑块组明显减少,平滑肌细胞较不稳定斑块组增多,其中复方组巨噬细胞减�Objective It is to investigate whether Qidan Tongmai tablet can interfere with the formation of atherosclerotic vulnerable plaques in ApoE-/-mice by inhibiting the activation of NLRP3 inflammasome.Methods The mice were randomly divided into control group,unstable plaque group,Yiqi group,Huoxue group and compound group,with 12 mice in each group.During the experiment,the mice in the control group were fed with ordinary feed,and the other groups were fed with high-fat feed;at the same time,the Yiqi group was given astragalus extract dry powder solvent(0.52 g crude drug/kg),and the Huoxue group was given Danshen extract dry powder solvent(1.31 g crude drug/kg),the compound group was given Qidan Tongmai tablet extract dry powder solvent(2 g crude drug/kg),and the control group and the unstable plaque group were given an equal volume of normal saline,all once a day.After continuous gavage for 14 d,the right carotid artery external catheterization was performed on the mice in each group,and the original intervention was continued for 12 weeks after the operation.After the intervention,the mice were anesthetized,their eyeballs were removed,and blood was collected.The levels of interleukin-1β(IL-1β)and interleukin-18(IL-18)in peripheral blood were detected by ELISA.The common carotid artery was isolated,the stability of carotid plaque in mice were observed by HE staining and CD68 andα-actin immunofluorescence staining;the expression of NLRP3 and Caspase-1 mRNA in plaque tissue was detected by RT-PCR,and the expression of plaque NLRP3 and Caspase-1 protein in block tissue was detected by Western blot.Results The levels of serum IL-1βand IL-18 in the unstable plaque group were significantly higher than those in the control group(all P<0.05);the levels of serum IL-1βand IL-18 in the Yiqi group,the Huoxue group and the compound group were significantly lower than those in the unstable plaque group(all P<0.05),and the compound group were significantly lower than the Yiqi group and the Huoxue group(all P<0.05),there was n

关 键 词：芪丹通脉片 NLRP3炎症小体 动脉粥样硬化 易损斑块 

分 类 号：R-332[医药卫生]