桂枝茯苓丸逆转ApoE^(-/-)小鼠动脉粥样硬化斑块机制研究  

Study on the Mechanism of Guizhi Fuling Pill on Reversing Atherosclerotic Plaque in ApoE^(-/-)Mice

作　　者：张婷 王丹 刘华坤[3] 李红星 张培法 刘震 韩文舫 何爱国 蔚红霞 ZHANG Ting;WANG Dan;LIU Huakun;LI Hongxing;ZHANG Peifa;LIU Zhen;HAN Wenfang;HE Aiguo;YU Hongxia(Department of Traditional Chinese Medicine,Jining Hospital of Integrated Traditional Chinese and Western Medicine,Jining 272000,China;School of Forensic Medicine and Medical Laboratory,Jining Medical College,Jining 272067,China;Department of Neurology,Jining First People's Hospital,Jining 272011,China;Department of Traditional Chinese Medicine,Jining Public Health Medical Center,Jining 272000,China)

机构地区：[1]济宁市中西医结合医院中医科,山东济宁272000 [2]济宁市医学院法医学与医学检验学院,山东济宁272067 [3]济宁市第一人民医院神经内科,山东济宁272011 [4]济宁市公共卫生医疗中心中医科,山东济宁272000

出　　处：《中西医结合研究》2025年第2期98-103,共6页Research of Integrated Traditional Chinese and Western Medicine

基　　金：山东省中医药科技项目(No.M-2022068);全国名老中医药专家传承工作室建设项目(No.国中医药人教函[2022]75号)。

摘　　要：目的探究桂枝茯苓丸逆转载脂蛋白e基因敲除(apolipoprotein e gene knockout,ApoE^(-/-))小鼠动脉粥样硬化斑块的作用机制。方法高脂饮食建立ApoE^(-/-)小鼠动脉粥样硬化模型,分为模型组、阿托伐他汀组、桂枝茯苓丸组、阿托伐他汀+桂枝茯苓丸组。通过油红O染色和苏木精-伊红(hematoxylin and eosin,HE)染色观察动脉粥样硬化病变后主动脉病理形态变化及各组药物对斑块的影响。采用免疫组织化学染色测定小鼠主动脉根部斑块内α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、转化生长因子-β1(transforming growth factor-β1,TGF-β1)及血管内皮生长因子(vascular endothelial growth factor,VEGF)表达量。结果①光镜下观察ApoE^(-/-)小鼠血管管腔明显狭窄,管腔内可见突起的斑块,内膜内泡沫细胞堆积,平滑肌紊乱,向内膜迁移,有明显的动脉粥样硬化形成。②与模型组相比,桂枝茯苓丸组、阿托伐他汀+桂枝茯苓丸组主动脉斑块面积明显缩小(P<0.01)。③与模型组相比,桂枝茯苓丸组、阿托伐他汀+桂枝茯苓丸组主动脉根部斑块VEGF表达阳性面积明显缩小(P<0.01)。④各组主动脉根部斑块TGF-β1、α-SMA均未出现阳性表达。结论桂枝茯苓丸可改善管腔狭窄,稳定血管结构,逆转动脉粥样硬化斑块形成。桂枝茯苓丸可能通过减少斑块局部VEGF表达,达到抑制动脉粥样硬化进程的作用。Objective To explore the mechanism of Guizhi Fuling pill in reversing atherosclerotic plaque in apolipoprotein e gene knockout(ApoE^(-/-))mice.Methods The atherosclerosis model of ApoE^(-/-)mice was established by high-fat diet,which was divided into model group,atorvastatin group,Guizhi Fuling pill group,atorvastatin+Guizhi Fuling pill group.The pathological changes of aorta after atherosclerotic lesions and the effects of each group of drugs on plaque were observed by oil red O staining and hematoxylin and eosin(HE)staining.Immunohistochemical staining was used to determine the expression ofα-smooth muscle actin(α-SMA),transforming growth factor-β1(TGF-β1)and vascular endothelial growth factor(VEGF)in mouse aortic root plaques.Results①Under the light microscope,the vascular lumen of ApoE^(-/-)mice was obviously narrowed,with protruding plaques in the lumen,accumulation of foam cells in the intima,disorder of smooth muscle,migration to the intima,and obvious atherosclerosis.②Compared with the model group,the aortic plaque area of the Guizhi Fuling pill group and the atorvastatin+Guizhi Fuling pill group was significantly reduced(P<0.01).③Compared with the model group,the positive area of VEGF expression in aortic root plaque in Guizhi Fuling pill group and atorvastatin+Guizhi Fuling pill group was significantly reduced(P<0.01).④There was no positive expression of TGF-β1 andα-SMA in aortic root plaques in each group.Conclusion Guizhi Fuling pill could improve luminal stenosis,stabilize vascular structure and reverse atherosclerotic plaque formation.Guizhi Fuling pill might inhibit the process of atherosclerosis by reduce the local expression of VEGF in plaque.

关 键 词：桂枝茯苓丸 ApoE^(-/-)小鼠 动脉粥样硬化斑块 血管内皮生长因子 

分 类 号：R285.5[医药卫生—中药学]