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心痛泰对痰瘀互结证腹主动脉易损斑块模型兔病理性血管新生及HIF-1α/VEGF/VEGFR2信号通路的影响 被引量:2

Effects of Xintongtai(心痛泰)on Pathological Angiogenesis and HIF-1α/VEGF/VEGFR2 Signaling Path⁃way in Abdominal Aortic Vulnerable Plaque Model Rabbits with Binding of Phlegm and Stasis Syndrome
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摘要 目的探讨心痛泰治疗动脉粥样硬化痰瘀互结证的可能作用机制。方法将60只清洁级兔随机分为假手术组、模型组、氟伐他汀组及心痛泰低、中、高剂量组,每组10只。除假手术组外,其余各组兔采用高脂喂养+腹主动脉球囊损伤法建立痰瘀互结证腹主动脉易损斑块模型。造模后心痛泰低、中、高剂量组分别给予心痛泰含生药1.87、3.73、7.46 g/(kg·d)灌胃,氟伐他汀组给予氟伐他汀钠缓释片1.87 mg/(kg·d)灌胃,假手术组和模型组给予10 ml/d超纯水灌胃,各组均连续灌胃8周。采用HE染色观察易损斑块中病理性血管新生的变化;采用痰瘀互结证中医证候评分表进行证候评分并计算总积分;测定斑块成分(包括细胞外脂质、泡沫细胞、胶原成分、平滑肌细胞各占所在斑块面积的百分比),并计算斑块易损指数;免疫组化法测定斑块组织中缺氧诱导因子1α(HIF-1α)、血管内皮生长因子(VEGF)、血管内皮生长因子受体2(VEGFR2)、血管生成素2(Ang-2)、成纤维细胞生长因子(FGF)阳性表达;蛋白免疫印迹法测定斑块组织中HIF-1α、VEGF、VEGFR2、Ang-2、FGF蛋白表达。结果HE染色显示,假手术组腹主动脉无斑块形成;模型组可见动脉弹力层破坏,形成易损斑块,内膜下有明显的泡沫细胞,斑块纤维帽破裂;与模型组相比,心痛泰各剂量组和氟伐他汀组斑块组织处的空泡化明显减轻,动脉内膜和斑块的结构更加稳定。与模型组比较,心痛泰各剂量组和氟伐他汀组各证候评分及总积分下降,细胞外脂质含量、泡沫细胞含量降低,胶原含量、平滑肌细胞含量增加,斑块易损指数降低,斑块组织中HIF-1α、VEGF、VEGFR2、Ang-2、FGF阳性表达及蛋白表达降低(P<0.05或P<0.01);且心痛泰中、高剂量组和氟伐他汀组各指标改善优于心痛泰低剂量组(P<0.01)。心痛泰中、高剂量组和氟伐他汀组组间两两比较,各指标差异无统计学意义(P>0.05)� Objective To explore the possible mechanism of Xintongtai(心痛泰)in treating atherosclerosis with binding of phlegm and stasis syndrome.Methods Sixty clean rabbits were randomly divided into sham operation group,model group,fluvastatin group and Xintongtai low-,medium-and high-dose groups,with 10 rabbits in each group.Except for the sham operation group,rabbits were given high-fat feeding plus balloon injury of abdominal aorta to establish the vulnerable plaque model of abdominal aorta with binding of phlegm and stasis syndrome.After model⁃ling,Xintongtai low-,medium-,and high-dose groups were given Xintongtai containing 1.87,3.73,and 7.46 g/(kg·d)of crude drug by gavage,while the fluvastatin group was given 1.87 mg/(kg·d)of fluvastatin sodium sus⁃tained-release tablets by gavage,and the sham operation group and the model group were given intragastric administra⁃tion of 10 ml/d of ultrapure water,all for 8 weeks.HE staining was used to observe the changes of pathological angio⁃genesis in vulnerable plaques.The traditional Chinese medicine(TCM)syndrome scale for binding of phlegm and stasis syndrome was used to evaluate the syndromes and calculate the total score.The plaque components including the per⁃centage of extracellular lipids,foam cells,collagen components and smooth muscle cells in the plaque area were mea⁃sured,and the plaque vulnerability index was calculated.Immunohistochemical method was used to detect the posi⁃tive expressions of hypoxia-inducible factor 1α(HIF-1α),vascular endothelial growth factor(VEGF),vascular endo⁃thelial growth factor receptor 2(VEGFR2),angiopoietin 2(Ang-2),and fibroblast growth factor(FGF)in the plaque tissue.Western blotting was used to detect HIF-1α,VEGF,VEGFR2,Ang-2,FGF protein expression.Results HE staining showed that there was no plaque in the abdominal aorta in the sham operation group;in the model group,the elastic layer of the arteries was damaged,forming vulnerable plaques,and there were obvious foam cells under the intima,and the fibrous cap
作者 易琼 彭清华 郭志华 李雅 魏佳明 彭筱平 YI Qiong;PENG Qinghua;GUO Zhihua;LI Ya;WEI Jiaming;PENG Xiaoping(The First Hospital of Hunan University of Chinese Medicine,Changsha,410007;Hunan University of Chinese Medicine;The First Affiliated Hospital of Hunan Traditional Chinese Medical College)
出处 《中医杂志》 CSCD 北大核心 2023年第2期159-166,共8页 Journal of Traditional Chinese Medicine
基金 湖南省自然科学基金(2021JJ30492,2021JJ40426) 湖南省中医药科研项目重点项目(2021029) 湖南省教育厅科学研究重点项目(20A384) 湖南中医药大学中医学一流学科开放基金项目(2021ZYX19,2021ZYX14) 湖南中医药大学中医学国内一流建设学科项目(湘教通[2018]469号)。
关键词 动脉粥样硬化 易损斑块 病理性血管新生 心痛泰 痰瘀互结证 atherosclerosis vulnerable plaque pathological angiogenesis Xintongtai(心痛泰) binding of phlegm and stasis syndrome
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