活心丸(浓缩丸)下调TLR4/TNF-α表达减轻ApoE^(-/-)小鼠动脉粥样硬化  

Huoxin pill(concentrated pill)alleviates atherosclerosis in ApoE^(-/-)mice by down-regulating TLR4/TNF-αexpression

作　　者：郑标 牙侯弟 余思君 全嘉锟 钟巧青[3] 莫中成 ZHENG Biao;YA Houdi;YU Sijun;QUAN Jiakun;ZHONG Qiaoqing;MO Zhongcheng(Guangxi Key Laboratory of Diabetic Systems Medicine,Department of Histology and Embryology,Guilin Medical University,Guilin 541199,China;College of Intelligent Medicine and Biotechnology,Guilin Medical University,Guilin 541199,China;Department of Cardiovascular Medicine,Xiangya Hospital,Central South University,Changsha 410008,China)

机构地区：[1]桂林医学院广西糖尿病系统医学重点实验室/组织胚胎学教研室,桂林541199 [2]桂林医学院智能医学与生物技术学院,桂林541199 [3]中南大学湘雅医院心血管内科,长沙410008

出　　处：《华夏医学》2024年第1期61-68,共8页Acta Medicinae Sinica

基　　金：国家自然科学基金项目(82060091);自治区级大学生创新创业训练计划项目(S202110601126);北京科创鼎诚医药科技有限公司横向科研课题。

摘　　要：目的探讨活心丸(浓缩丸)对载脂蛋白E基因敲除(ApoE^(-/-))小鼠动脉粥样硬化(As)的影响及机制。方法选取ApoE^(-/-)小鼠,饲以高脂饮食复制As模型,采用不同浓度活心丸和(或)Toll样受体4(TLR4)抑制剂处理,随机分为对照组、活心丸处理组、TLR4抑制剂处理组、活心丸和TLR4抑制剂共处理组。苏木素-伊红(HE)染色、马松(Masson)染色观察As模型鼠主动脉窦病变情况;油红O(ORO)染色观察As模型鼠主动脉窦及主动脉脂质蓄积情况;免疫组织化学法(IHC)检测As模型鼠主动脉窦TLR4、肿瘤坏死因子α(TNF-α)表达情况。结果与对照组比较,活心丸减轻As模型鼠主动脉窦病变,减少主动脉病变处脂质蓄积,降低主动脉窦狭窄程度,差异均有统计学意义(P<0.05);活心丸还下调As模型鼠主动脉窦TLR4和TNF-α表达(P<0.05),TLR4抑制剂与活心丸作用具有协同性。结论活心丸可以减轻ApoE^(-/-)小鼠As病变,其机制可能与下调TLR4、TNF-α表达以及调控炎症反应相关。Objective To investigate the effect and mechanism of Huoxin pill(concentrated pill)on atherosclerosis(As)in apolipoprotein E knockout(ApoE^(-/-))mice.Methods ApoE^(-/-)mice were fed with high-fat diet to replicate As model.The mice were treated with different concentrations of Huoxin pills and Toll-like receptor 4(TLR4)inhibitor.The mice were randomly divided into control group,Huoxin pill treatment group,TLR4 inhibitor treatment group,and Huoxin pill and TLR4 inhibitor co-treatment group.Hematoxylin-eosin(HE)staining and Masson staining were used to observe the pathological changes of aortic sinus of As model mice.Oil red O(ORO)staining was used to observe the lipid accumulation in aortic sinus and aorta of As model mice.Immunohistochemistry was used to detect the expression of TLR4 and tumor necrosis factor-α(TNF-α)in aortic sinus of As model mice.Results Compared with the control group,Huoxin pills significantly reduced the aortic sinus lesions,reduced the lipid accumulation in the aortic lesions and the degree of aortic sinus stenosis of As model mice,with a statistically significant difference(P<0.05).In addition,Huoxin pills also down-regulated the expression of TLR4 and TNF-αin aortic sinus of As model mice(P<0.05),and the effect of TLR4 inhibitor and Huoxin pills had a synergistic effect.Conclusion Huoxin pills can alleviate As in ApoE^(-/-)mice and its mechanism may be related to down-regulating the expression of TLR4 and TNF-αand regulating the inflammatory response.

关 键 词：活心丸 动脉粥样硬化 TOLL样受体4 肿瘤坏死因子α 

分 类 号：R589[医药卫生—内分泌]