ApoE^-/-小鼠动脉粥样硬化模型的中医证型

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,差异有统计学意义(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。

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

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).Compared 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.