Page 54 - 《中国药房》2021年22期

基于 TLR4/NF-κB 信号通路探究心脉康改善兔动脉粥样硬化的

机制 Δ

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周智慧 ，陈 贺 ，吴锦波 ，叶小汉 （1.广州中医药大学东莞医院心内科，广东 东莞 523015；2.广州中医药大
1＊
1 #
学第一临床医学院，广州 510405）
中图分类号 R972 文献标志码 A 文章编号 1001-0408（2021）22-2736-07
DOI 10.6039/j.issn.1001-0408.2021.22.09
摘 要 目的：探究心脉康改善兔动脉粥样硬化（AS）的机制。方法：将50只雄性新西兰兔随机分为假手术组、模型组、辛伐他汀
组[阳性对照，2.60 mg/（kg·d）]和心脉康低、高剂量组[0.21、0.84 g/（kg·d）]，每组10只。假手术组兔给予普通饲料喂养，只分离结
扎股动脉但不损伤腹主动脉内皮；其余各组兔均给予高脂饲料喂养并行腹主动脉内膜球囊损伤术以复制AS模型。术后10周，假
手术组和模型组兔均灌胃生理盐水，各药物组兔灌胃相应药液（溶剂均为生理盐水），给药体积为100 mL，每天给药1次，连续12
周。末次给药后，观察各组兔腹主动脉及内壁的病理变化，检测血清中三酰甘油（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇
（LDL-C）、高密度脂蛋白胆固醇（HDL-C）以及白细胞介素 6（IL-6）、IL-1β含量，检测腹主动脉组织中 Toll 样受体 4（TLR4）、核因
子κB p65（NF-κB p65）含量及其蛋白表达水平。结果：与假手术组比较，模型组兔腹主动脉管腔内膜富含脂质，管壁厚度和斑块面
积明显增加，可见明显的血管内皮损伤；血清中TG、TC、LDL-C、IL-6、IL-1β含量和腹主动脉组织中TLR4、NF-κB p65含量及其蛋
白表达水平均显著升高，HDL-C含量显著降低（P＜0.05或P＜0.01）。与模型组比较，心脉康高剂量组和辛伐他汀组兔腹主动脉
病变减轻，且内壁未见明显损伤，其TG、TC、LDL-C、IL-6、IL-1β含量以及心脉康低剂量组NF-κB p65含量和TLR4、NF-κB p65蛋
白表达水平均显著改善（P＜0.05或P＜0.01）。结论：心脉康可改善兔AS，其机制可能与下调TLR4、NF-κB p65表达，抑制炎症反
应有关。
关键词 心脉康；动脉粥样硬化；Toll样受体家族4/核因子κB信号通路；血脂代谢；炎症反应；兔

Study on Mechanism of the Improvement Effects of Xinmaikang on Atherosclerosis in Rabbits Based on
TLR4/NF-κB Signaling Pathway
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ZHOU Zhihui ，CHEN He ，WU Jinbo ，YE Xiaohan（1. Dept. of Cardiology，Dongguan Hospital，Guangzhou
1
University of TCM，Guangdong Dongguan 523015，China；2. The First Clinical Medical College，Guangzhou
University of TCM，Guangzhou 510405，China）
ABSTRACT OBJECTIVE：To explore the mechanism of Xinmaikang improving atherosclerosis（AS）in rabbits. METHODS：A
total of 50 male Zealand rabbits were randomly divided into sham operation group，model group，simvastatin group [positive control，
2.60 mg/（kg·d）] and Xinmaikang low-dose and high-dose groups [0.21，0.84 g/（kg·d）]，with 10 rabbits in each group. Rabbits in
sham operation group were fed with ordinary diet，and only femoral artery was separated and ligated，and abdominal aortic
endothelium was not strained；the other groups were given high-fat diet and received abdominal aortic intimal balloon injury to
induce AS model. Ten weeks after operation，sham operation group and model group were given intragastric administration of
normal saline，and administration groups were given corresponding drug solution intragastrically（normal saline as solvent）with the
volume of 100 mL，once a day，for consecutive 12 weeks. After last administration，the pathological changes of abdominal aorta
and inner wall in rabbits were observed in each group. The serum contents of triglyceride（TG），total cholesterol（TC），low
density lipoprotein cholesterol （LDL-C），high density lipoprotein cholesterol （HDL-C），interleukin-6（IL-6） and IL-1 β were
detected，and the contents and protein expression of Toll-like receptor 4 （TLR4） and nuclear factor-κ B p65 （NF-κ B p65） in
abdominal aortic tissue were determined. RESULTS：Compared with sham operation group，the intima of abdominal aorta in model
group was rich in lipids，the thickness of vessel wall and plaque area were increased obviously，and there was obvious vascular
endothelial injury. The contents of TG，TC，LDL-C，IL-6 and IL-1β in serum，the contents and protein expression of TLR4 and NF-κB
p65 in abdominal aorta tissue were significantly increased，while the content of HDL-C was decreased significantly（P＜0.05 or P＜
0.01）. Compared with model group，the lesion of rabbit abdominal aorta were alleviated，and no obvious damage was found on the
inner wall. The contents of TG，TC，LDL-C，IL-6，IL-1β of
Δ 基金项目：广东省中医药局科研项目（No.20184019）
Xinmaikang high-dose group and simvastatin group as well as
＊硕士研究生。研究方向：中西医结合治疗心血管疾病。E-mail：
the content of NF-κB p65 and protein expression of TLR4 and
1401398147@qq.com
# 通信作者：主任中医师。研究方向：心血管内科。E-mail：cnd- NF-κB p65 were improved significantly（P＜0.05 or P＜0.01）.
gyxh@163.com CONCLUSIONS： Xinmaikang can improve AS in rabbits，

·2736 · China Pharmacy 2021 Vol. 32 No. 22 中国药房 2021年第32卷第22期