白云绮 李慧 宋珂 王淑琪 高照 孙克寒 金秋硕 娄利霞 吴爱明 吴圣贤 聂波

摘要 目的：探讨长期高脂饲养ApoE-/-小鼠中医的证型，为抗动脉粥样硬化证候中药的研究提供证型动物模型。方法：将20只雄性ApoE-/-小鼠按随机数字表法分为四妙勇安汤组（SM组）和模型组（M组），每组10只，采用高脂饲料喂养14周建立动脉粥样硬化模型，SM组于造模开始进行预防性给药。同时以C57BL/6小鼠10只作为正常对照组（N组）。检测血清总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）水平，观察主动脉和肝脏病理，评价是否为血瘀痰湿证型;通过IL-6、核因子-κB免疫组织化学变化评价是否为毒损证型。结果：与N组比较，M组小鼠血清TC、TG、LDL-C显著提高，HDL-C显著降低，差异有统计学意义（P<0.05）;肝脏病理出现球形脂滴及炎性细胞浸润;主动脉出现明显斑块，血管内膜厚度（IT）、中膜厚度（MT）、斑块面积（PA）及IT/MT明显增大，差异有统計学意义（P<0.05），血管管腔面积（LA）明显减小，差异有统计学意义（P<0.05）;免疫组织化学显示IL-6、核因子-κB在主动脉的表达明显增加，差异有统计学意义（P<0.05）。与模型组比较，SM组能够明显降低ApoE-/-小鼠主动脉PA、IT及IT/MT，明显降低IL-6及核因子-κB表达，差异有统计学意义（P<0.05）;减轻肝脏病变;但对血脂水平无明显作用。结论：长期高脂饲料饲养ApoE-/-小鼠制备的动脉粥样硬化模型为痰湿血瘀毒损型病证结合动物模型。

关键词 动脉粥样硬化;ApoE-/-小鼠;病证结合动物模型;痰湿血瘀毒损;四妙勇安汤

Preliminary Study on TCM Syndromes of ApoE-/-Mouse Atherosclerosis Model

BAI Yunqi1，LI Hui2，SONG Ke1，WANG Shuqi2，GAO Zhao1，SUN Kehan2，JIN Qiushuo1，LOU Lixia1，WU Aiming1，WU Shengxian1，NIE Bo1，2

（1 Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing，Dongzhimen Hospital，Beijing University of Chinese Medicine，Beijing 100700，China; 2 School of Chinese Materia Medica，Beijing University of Chinese Medicine，Beijing 100029，China）

Abstract Objective：To explore the long-term high-fat feeding of ApoE-/-mice with TCM syndrome types，and provide animal models for the research of anti-atherosclerosis syndromes in traditional Chinese medicine.Methods：A total of 20 male ApoE-/-mice were divided into Simiao Yongan Decoction group （SM group） and model group （M group） according to the random number table method.10 mice in each group were fed with high-fat diet for 14 weeks to establish atherosclerosis model.Meanwhile，the SM group started preventive administration at the time of modeling.At the same time，10 mice of C57BL / 6 were used as the normal control group （group N）.By measuring serum total cholesterol （TC），triglyceride （TG），high-density lipoprotein cholesterol （HDL-C），and low-density lipoprotein cholesterol （LDL-C） levels，observing aorta and liver pathology to evaluate whether it was the blood stasis phlegm-dampness syndrome type; evaluating whether it was a poisonous syndrome type by the changes of IL-6 and NF-κB immunohistochemical.Results：Compared with the control group，the serum levels of TC，TG，and LDL-C in the model group were significantly increased （P<0.01），HDL-C was significantly reduced （P<0.01）; spherical lipid droplets and inflammatory cell infiltration appeared in the liver pathology; obvious plaques appeared in the aorta; aortic intima thickness （IT），media thickness （MT），plaque area （PA），and IT / MT significantly increased （P<0.01），and the vascular lumen area （LA） decreased significantly （P<0.01）; immunohistochemistry showed that the expression of IL-6 and NF-κB in the aorta was significantly increased （P<0.05）.com

pared with the model group，the SM group can significantly reduce the aorta PA，IT and IT / MT of ApoE-/-mice （P<0.05），and significantly reduce the expression of IL-6 and NF-κB （P<0.05）; it also reduced liver disease but had no significant effect on blood lipid levels.Conclusion：The atherosclerosis model prepared by the classic long-term high-fat feed ApoE-/-mice was preliminary evaluated as an animal model of phlegm dampness and blood stasis and toxin damage.

Keywords Atherosclerosis; ApoE-/-mice; Disease combined syndrome animal model; Phlegm dampness blood stasis toxin damage; Simiao Yongan Decoction

中圖分类号：R285.5文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.01.011

心脑血管疾病发展的主要病理基础是动脉粥样硬化（Atherosclerosis，AS）。AS属于中医的“脉痹”“胸痹”“眩晕”“中风”等病证，既往医家将AS概括为“虚”“瘀”“痰”“毒”四证[1-3]，并将AS辨证分型暂分为气滞血瘀证、痰瘀互结证、气虚血瘀证、气阴两虚证4种[3]。痰湿、血瘀、毒损始终贯穿动脉粥样硬化整个病程[4-6]。研究痰湿血瘀毒损型AS模型对于AS的中医治疗具有重要意义。长期高脂饲料饲养喂养ApoE-/-小鼠是建立AS动物模型的经典方法，已经被广泛研究并应用于AS的发病机制、药物防治等方面[7]，但尚未见有关该经典模型的中医证型研究报道。因此，本研究以长期高脂饲料饲养ApoE-/-小鼠……