动脉粥样硬化(气滞血瘀证)病证结合大鼠模型的研究  

A study on a rat model of atherosclerosis with qi stagnation and blood stasis syndrome

作　　者：郭文鹤 黄娜娜 张晓亮 李晓宇[3,4] 张家祥 齐晓甜 孙蓉 GUO Wenhe;HUANG Nana;ZHANG Xiaoliang;LI Xiaoyu;ZHANG Jiaxiang;QI Xiaotian;SUN Rong(The Second Hospital of Shandong University,Jinan 250033,China;Center of Life Science and Environmental Science,Harbin University of Commerce,Harbin 150076;Shandong University of Traditional Chinese Medicine,Jinan 250355;Shandong Academy of Chinese Medicine,Jinan 250014;Institute of Advanced Medical Sciences,Shandong University,Jinan 250012)

机构地区：[1]山东大学第二医院,济南250033 [2]哈尔滨商业大学生命科学与环境科学研究中心,哈尔滨150076 [3]山东中医药大学,济南250355 [4]山东省中医药研究院,济南250014 [5]山东大学高等医学研究院,济南250012

出　　处：《中国比较医学杂志》2019年第9期32-41,80,共10页Chinese Journal of Comparative Medicine

基　　金：山东省重大产业专项:国家基药大品种心可舒片二次深度开发(2015ZDZX07002);山东省自主创新和成果转化课题(2014ZZCX02104);泰山学者工程专项经费资助(Ns201511107)

摘　　要：目的构建动脉粥样硬化(气滞血瘀证)病证结合的大鼠模型,为相应中药复方的药效学研究提供评价工具。方法参照相关资料及文献研究,抽提出评价动脉粥样硬化(气滞血瘀证)大鼠模型的诊疗指标,并以辛伐他汀片和通脉颗粒作为反证药物。结合动脉粥样硬化病因病机的演变规律、发病机制的现代研究,拟选用冰水浴、灌胃脂肪乳和尾静脉注射牛血清蛋白复合诱导方法制备动脉粥样硬化(气滞血瘀证)大鼠病证结合模型。实验期间,考察各组别大鼠的症状、体征状况并赋分。造模8周后,检测各组别大鼠血脂、凝血四项水平,升主动脉病理变化,进行成模预检测。造模成功后,用反证药物干预,并测定大鼠的血脂、凝血四项水平,检测升主动脉和肝组织的病理学变化。结果造模21周后,与正常组相比,模型组大鼠的症状和体征变化明显,血脂水平和纤维蛋白原含量非常显著升高,活化部分凝血酶原时间显著降低。升主动脉内膜下出现脂质沉积,肝细胞出现空泡、变性,基本符合动脉粥样硬化(气滞血瘀证)的临床表现。药物干预后,与模型组相比,药物反证组大鼠血脂水平和纤维蛋白原含量显著下降,升主动脉内膜和肝组织未见明显异常。结论冰水浴、灌胃脂肪乳及尾静脉注射牛血清蛋白复合诱导方法连续造模21周,可建立模拟临床动脉粥样硬化(气滞血瘀证)的大鼠模型,并具备成模率高、与临床症状和体征表现相近等特点,这将为抗动脉粥样硬化(气滞血瘀证)中药复方的药效学研究提供评价载体。Objective To establish a rat model of atherosclerosis with qi stagnation and blood stasis syndrome,to provide an evaluation tool for a pharmacodynamic study of Traditional Chinese Medicine formulas.Methods According to relevant materials and references,we extracted diagnosis and treatment indicators for evaluating rat models of atherosclerosis with qi stagnation and blood stasis syndrome.Simvastatin tablets and Tongmai granules were used as verification drugs.Based on the etiology and pathogenesis together with modern research on the pathogenesis of atherosclerosis,we used co-induction method in an ice-water bath,followed by fat emulsion gavage and injection of bovine serum albumin via the tail vein,to establish a rat model of atherosclerosis with qi stagnation and blood stasis syndrome.We examined the symptoms and signs and assessed the scores of rats in each group.We also measured the blood lipids and coagulation levels,detected the pathological changes in the ascending aorta of rats in each group after 8 weeks,and performed model establishement pre-testing.After the model was successfully established,intervention with verification drugs was performed,and the blood lipids and the coagulation levels were measured,followed by examination of the pathological changes in ascending aorta and hepatic tissue of the rats.Results After 21 weeks,the rats’symptoms and signs were significantly altered,the blood lipid levels and fibrinogen levels were significantly increased,the activated partial prothrombin duration was significantly reduced,and lipid deposition occurred in the ascending aorta intima.Furthermore,we observed vacuolation and degeneration of hepatocytes,which was consistent with the clinical manifestations of atherosclerosis with qi stagnation and blood stasis syndrome.Compared with the model group,the blood lipids level and fibrinogen content were significantly decreased,and no obvious abnormalities were found in the ascending aorta intima and hepatic tissue of rats in the drug-verification group.Conclusion

关 键 词：动脉粥样硬化 气滞血瘀证 病证结合 大鼠模型 

分 类 号：R-33[医药卫生]