中国组织工程研究 ›› 2016, Vol. 20 ›› Issue (18): 2703-2710.doi: 10.3969/j.issn.2095-4344.2016.18.018

• 心脏及血管损伤动物模型 Animal models of heart and vascular damage • 上一篇    下一篇

动脉粥样硬化模型大鼠主动脉Rho激酶及相关细胞因子表达与益气活血方的干预

张红珍1,焦 瑞2,李 丽2,张 英2,钱 艳2,郭春兰1   

  1. 1山西中医学院中西医结合临床学院,山西省太原市  030619;2山西医科大学,山西省太原市  030001
  • 收稿日期:2016-03-13 出版日期:2016-04-29 发布日期:2016-04-29
  • 通讯作者: 郭春兰,硕士,讲师,山西中医学院中西医结合临床学院,山西省太原市 030619
  • 作者简介:张红珍,女,1968年生,汉族,2005年山西医科大学毕业,硕士,教授,主要从事中西医结合防治动脉粥样硬化基础及临床研究。
  • 基金资助:

    国家自然科学基金资助项目(81373532)

Effects of Qi-Benefiting Blood-Activating Chinese herbs on aorta Rho kinase and related cytokine expression in a rat model of atherosclerosis

Zhang Hong-zhen1, Jiao Rui2, Li Li2, Zhang Ying2, Qian Yan2, Guo Chun-lan1   

  1. 1Clinical School of Integrated Traditional Chinese and Western Medicine, Shanxi University of Traditional Chinese Medicine, Taiyuan 030619, Shanxi Province, China; 2Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
  • Received:2016-03-13 Online:2016-04-29 Published:2016-04-29
  • Contact: Guo Chun-lan, Master, Lecturer, Clinical School of Integrated Traditional Chinese and Western Medicine, Shanxi University of Traditional Chinese Medicine, Taiyuan 030619, Shanxi Province, China
  • About author:Zhang Hong-zhen, Master, Professor, Clinical School of Integrated Traditional Chinese and Western Medicine, Shanxi University of Traditional Chinese Medicine, Taiyuan 030619, Shanxi Province, China
  • Supported by:

    the National Natural Science Foundation of China, No. 81373532

摘要:

文章快速阅读:

 

文题释义:
Rho激酶:是一种丝/苏氨酸蛋白激酶,是最早发现的Rho效应物,也是目前研究最清楚的一个RhoA下游效应分子,可通过调节组织因子、基质金属蛋白酶等细胞因子的合成与表达,促进动脉粥样硬化的发生、发展,由日本和新加坡先后鉴别,国内外研究已确认Rho激酶对于动脉硬化的形成、发生、发展具有非常重要的作用。
基质金属蛋白酶:从初始内膜增厚到最终斑块破裂相等动脉粥样斑块病变各时期中都扮演了重要角色,不同亚型基质金属蛋白酶在动脉粥样硬化病变有不同作用。基质金属蛋白酶2和基质金属蛋白酶9在血管壁对内膜损伤的反应和动脉粥样硬化形成过程中起关键作用,并通过与血管平滑肌细胞作用干预血管的重构,影响动脉粥样硬化病程的发展及并发症的产生。
 
背景:益气活血的代表方剂补阳还五汤能够改善微循环,改善组织缺氧;降低纤维蛋白原、抗血小板聚集;降低血脂;扩张血管;抗血栓形成,减少新生斑块的破裂,具有多靶点、多途径抗动脉粥样硬化作用。

目的:观察益气活血法的代表方剂补阳还五汤对动脉粥样硬化大鼠模型主动脉Rho激酶、组织因子及基质金属蛋白酶2、基质金属蛋白酶9 mRNA表达的影响,探讨补阳还五汤抗动脉粥样硬化的作用机制。
方法:维生素D3加高脂饮食诱导大鼠动脉粥样硬化模型。60只大鼠随机分为正常对照组、模型组、补阳还五汤10 g/kg组、补阳还五汤20 g/kg组、辛伐他汀对照组及补阳还五汤预防组,每组10只。造模成功后干预28 d,检测主动脉Rho激酶、组织因子及基质金属蛋白酶2、基质金属蛋白酶9 mRNA表达及血脂水平。
结果与结论:①高脂饮食加维生素D3可诱导大鼠形成动脉粥样硬化模型,模型组有动脉粥样硬化斑块形成;②Rho激酶、组织因子及基质金属蛋白酶2、基质金属蛋白酶9 mRNA表达量及血脂水平:正常对照组、补阳还五汤20 g/kg组、辛伐他汀对照组、补阳还五汤预防组均显著低于模型组,差异有非常显著性意义(P < 0.01);补阳还五汤10 g/kg组也显著低于模型组,差异有显著性意义(P < 0.05);补阳还五汤预防组、补阳还五汤20 g/kg组、辛伐他汀对照组各组间差异无显著性意义(P > 0.05);③结果提示益气活血方剂补阳还五汤具有抗动脉粥样硬化作用,降低Rho激酶、组织因子及基质金属蛋白酶2、基质金属蛋白酶9 mRNA水平可能是其作用机制之一。

中国组织工程研究杂志出版内容重点:肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程 
ORCID: 0000-0002-1461-210X(张红珍)

关键词: 实验动物, 心肺损伤与修复动物模型, 益气活血, 补阳还五汤, 动脉粥样硬化, Rho激酶, 组织因子, 基质金属蛋白酶, 国家自然科学基金

Abstract:

BACKGROUND: Representative formulae of Qi-Benefiting and Blood-Activating Chinese medicinal herbs Bu Yang Huan Wu Tang (BYHWT) can improve microcirculation and hypoxia, decrease fibrinogen, resist platelet aggregation, reduce blood lipid, dilate blood vessel, resist thrombosis, and reduce neonatal plaque rupture, and has a multi-target, multi-channel anti-atherosclerotic effect. 

OBJECTIVE: To observe the influence of representative formulae of Qi-Benefiting and Blood-Activating Chinese medicinal herbs BYHWT on aorta Rho kinase, tissue factor, matrix metalloproteinase-2, matrix metalloproteinase-9 mRNA expression in atherosclerosis models, and to explore the action mechanism of BYHWT on anti-atherosclerosis. 
METHODS: Vitamin D3 and high fat diet induced atherosclerosis in rats. 60 rats were randomly divided into normal control group, model group, 10 g/kg BYHWT therapy group, 20 g/kg BYHWT therapy group, simvastatin control group and BYHWT prevention group (n=10). At 28 days after model establishment, the expression level of Rho kinase, tissue factor, matrix metalloproteinase-2, matrix metalloproteinase-9 mRNA expression and blood lipid level were detected.
RESULTS AND CONCLUSION: (1) High fat diet and vitamin D3 could induce atherosclerosis in rats. Atherosclerotic plaque formed in the model group. (2) Rho kinase, tissue factor, matrix metalloproteinase-2, matrix metalloproteinase-9 mRNA expression and blood lipid were significantly lower in the normal control group, 20 g/kg BYHWT therapy group, simvastatin control group and BYHWT prevention group than in the model group (P < 0.01). Above indexes were significantly lower in the 10 g/kg BYHWT therapy group than in the model group (P < 0.05). No significant difference in above indexes was detected among BYHWT prevention group, 20 g/kg BYHWT therapy group and simvastatin control group (P > 0.05). (3) Results indicated that Qi-Benefiting and Blood-Activating BYHWT can resist atherosclerosis, down-regulate the expression of Rho kinase, tissue factor, matrix metalloproteinase-2, and matrix metalloproteinase-9 mRNA expression, which may be one of the mechanisms of anti-atherosclerosis.
中国组织工程研究杂志出版内容重点:肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程 

Key words: Models, Animal, Atherosclerosis, Matrix Metalloproteinases, Cytokines, Tissue Engineering