文章摘要
桂枝茯苓丸逆转ApoE-/-小鼠动脉粥样硬化斑块疗效观察及机制研究
Study on the Mechanism of Guizhi Fuling Pill on reversing Atherosclerotic plaque in ApoE-/- mice
DOI:
中文关键词: 桂枝茯苓丸  ApoE-/-小鼠  动脉粥样硬化斑块  血管内皮生长因子
英文关键词: Guizhi Fuling pills  ApoE-/- mice  Atherosclerotic plaque  Vascular endothelial growth factor
基金项目:]山东省中医药科技项目(编号:M-2022068);全国名老中医药专家传承工作室建设项目(批文号:国中医药人教函〔2022〕75号)
作者单位邮编
p>张婷 济宁市中西医结合医院 272000
王丹 济宁市医学院 
刘华坤 济宁市第一人民医院 
李红星 济宁市中西医结合医院 
张培法 济宁市中西医结合医院 
刘震 济宁市中西医结合医院 
韩文舫 济宁市公共卫生医疗中心 
何爱国 济宁市中西医结合医院 
蔚红霞 济宁市中西医结合医院 
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中文摘要:
      目的 探究桂枝茯苓丸逆转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,分为模型对照组、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成功建立ApoE-/-小鼠模型: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。②ApoE-/-小鼠动脉粥样硬化斑块面积影响:与模型对照组相比,阿托伐他汀组斑块面积减少,但差异无统计学意义(P>0.05),桂枝茯苓丸组斑块内斑块面积缩小差异有统计学意义(P<0.01),而阿托伐他汀+桂枝茯苓丸组脉斑块缩小差异有统计学差异(P<0.01)。③ApoE-/-小鼠VEGF表达阳性面积的影响:空白对照组主动脉根部无VEGF表达;与模型对照组比较,阿托伐他汀+桂枝茯苓丸组阳性表达差异有统计学意义(P<0.01),桂枝茯苓丸组阳性表达差异有统计学意义(P<0.01),阿托伐他汀组阳性表达差异无统计学意义(P>0.05)。④各组ApoE-/-小鼠TGF-β1、α-SMA均未出现阳性表达。结论 桂枝茯苓丸可一定程度上改善管腔狭窄,稳定血管结构,抑制血管重构。西药加中成药可以增加逆转斑块疗效。桂枝茯苓丸可能通过减少斑块局部VEGF表达,达到抑制动脉硬化进程的作用。
英文摘要:
      Study on the Therapeutic effect and Mechanism of Guizhi Fuling Pill on reversing Atherosclerotic plaque in ApoE-/-mice. Methods The atherosclerotic model of ApoE-/-mice was established by high-fat diet, They were divided into model control group, Atto vastatin group, Guizhi Fuling pill group, Atto vastatin + Guizhi Fuling pill group.and Guizhi Fuling pills were given for intervention.Observation of pathomorphological changes of aorta after atherosclerosis by hematoxylin-eosin (HE) staining;And observe the curative effect of plaque.The expression of SM-αaction, transforming growth factor β 1 (TGF-β1) and vascular endothelial growth factor (vascular endothelial growth factor,VEGF) in smooth muscle cells of mouse aortic root plaques were detected by immunohistochemical staining. Results ApoE-/ mouse model was successfully established: under light microscope, the vascular lumen of ApoE-/- mice was obviously narrowed, protruding plaques could be seen in the lumen, foam cells accumulated in the intima, smooth muscle was disordered, migrated to the intima, and obvious arterial plaques were formed.Effect of atherosclerotic plaque area in ApoE-/- mice: compared with the model control group, the plaque area in the Atto vastatin group was smaller, but there was no significant difference (P < 0.05). The plaque area in the Guizhi Fuling pill group was significantly lower than that in the Guizhi Fuling pill group (P < 0.01). However, there was significant difference in the plaque reduction in the Atto vastatin + Guizhi Fuling pill group (P < 0.01).The influence of positive area of VEGF expression in ApoE-/- mice: there was no VEGF expression in aorta in normal control group; compared with the model control group,there was significant difference in the plaque reduction in the Atto vastatin + Guizhi Fuling pill group (P < 0.01).There was significant difference in positive expression between Guizhi Fuling pill group and Atto vastatin group (P < 0.05). There was no positive expression of TGF-β1 and α-SMA in all groups of ApoE-/- mice. Conclusion Compared with Atto vastatin group, Guizhi Fuling pill group significantly reduced the area of arterial plaque, suggesting that Guizhi Fuling pill can improve lumen stenosis, stabilize vascular structure and inhibit vascular remodeling to some extent.Western medicine plus proprietary Chinese medicine can increase the curative effect of reversing plaque. Guizhi Fuling Pill may inhibit the process of atherosclerosis by reducing the expression of VEGF in plaque.
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