摘要
目的:建立络气虚滞型血管内皮功能障碍病证结合动物模型,并观察不同类别通络方药的干预作用。方法:健康雄性Wistar大鼠随机分为对照组、同型半胱氨酸(HCY)组、络气虚滞组、人参组、双参(人参+丹参)组、通心络组。观察并记录大鼠的一般状况;检测血液中血管活性物质AngⅡ、ET、TXA2、PGI2、NO水平。免疫组织化学染色检测ACE、eNOS、AT1、ET-1在动脉组织中的表达;体外血管环实验检测大鼠胸主动脉内皮依赖性舒张反应。结果:①与对照组和HCY组比较,络气虚滞组大鼠精神萎靡,眼睑下垂,反应迟钝,毛发枯槁,体质量显著下降,皮下少有脂肪,甚至抓之触骨,鼻尾颜色苍白;耐力明显低于对照组。各治疗组大鼠一般情况有不同程度改善。②与对照组比较,HCY组大鼠血浆AngⅡ含量明显升高(P<0.01),而NO水平显著降低(P<0.05)。络气虚滞组大鼠血浆AngⅡ、ET、TXA2水平较对照组明显增高(P<0.001,P<0.05,P<0.001),而PGI2、NO含量则显著降低(P<0.01,P<0.001),其中AngⅡ含量明显高于HCY组(P<0.05)。与络气虚滞组比较,三种通络方药可不同程度降低血浆AngⅡ、ET水平(P<0.001,P<0.01,P<0.05),显著升高血清NO含量(P<0.01,P<0.05)。③络气虚滞组eNOS表达较对照组和HCY组明显减弱,而ACE、AT1、ET-1表达明显增强,三组通络方药可从不同程度上减弱ACE、AT1、ET-1表达,增强eNOS表达。④络气虚滞组体外血管环内皮依赖性舒张百分率较对照组显著降低(P<0.05,P<0.001)。与络气虚滞组比较,三种通络方药可使体外血管环舒张百分率不同程度上升(P<0.01,P<0.05,P<0.01)。结论:以蛋氨酸饮食复合"基础饮食+负重游泳"法建立的动物模型表现出的精神萎靡、反应迟钝、体质量下降等现象与临床络气虚滞血管内皮功能障碍患者证候特点基本吻合,同时血管内皮功能障碍较HCY组进一步加重,不同类别通络方药可使上述病证得到不同程度改善,提示所建立的络气虚滞型血管内皮功能障碍模型是成功的。
Objectives： to establish the animal model of combining the syndrome of endothelial dysfunction and stagnancy of collateral-Qi in a deficiency condition（SCQDC）. At the same time, the intervening mechanism of different kinds of herbs to dredge collateral was observed. Methods： healthy male Wistar rats of clearmess level were randomly devided into control group, the HCY group, the SCQDC group, the Renshen group, the Shuangshen group, the Tongxinluo group. The general condition of rats was observed each day. Tested the level of angiotensin Ⅱ （Ang Ⅱ ）, endothelin（ET）, thromboxane A2 （TXA2）, prostacyclin I2 （PGI2）, nitrogen monoxidum（NO）. Histochemieal stain method was used to analyze the angiotensin converting enzyme in aorta thoraciea tissue（ACE）and the expression of endothelium-typed nitrogen oxide synthase（eNOS ）, No. 1 receptor of angiotensin Ⅱ （AT1）, endothelin receptor（ ET-1 ）. The endothelial dependent diastolic percentages of blood vascularring in vitro was detected. Results： Ocompared with control group and HCY group, and all the rats in SCQDC group appeared the following symptoms： obvious hypodynamia, insensitive response, skin slacked, body weight decreased, fur on the back dimmed, nose and tail being erythroic and rarely lustrous, stool being soft and shaped. In addition, the endurance capacity was significantly less than that of the control group. The condition of the rats in all treatment groups was slighted improved. （Z） compared with the control group, the content of Ang Ⅱ in plasma of rats in the HCY group was significantly increased （P 〈 0.01 ）, while the content of NO was significantly decreased（P〈0.05）. The Ang Ⅱ, ET and TXA2 level in the SCQDC group was significantly increased than the level in the control group（P〈0. 001 ,P〈0.05,P〈0.001）.While the contents of PGI2 and NO in the SCQDC group were significantly decreased than the contents in the control group （P〈0.01）,the content of Ang Ⅱ in the SCODC group was much more increased than that in the HCY group（ P〈 0.05 ）. After giving the three kinds of herbs to dredge collateral, the Ang Ⅱ, ET level in plasma was significantly decreased when compared with the SCQDC group （P 〈 0.01, P 〈 0.05）, the content of NO was significantly increased（ P 〈 0.05 ）. Qthe immunohistochemieal stain analysis showed that the expression of ACE, AT1 ,ET-1 was enhanced, compared with the control group and the HCY group, the eNOS ex- pressions of the SCQDC group was significantly weakened, but the expression of AT1, ET-lwas obviously enhanced. Three different kinds of herbs to dredge collateral could weaken the expression of AT1, ET-1 and enhance the eNOS expression in different degree. ④ the diastolic reactivity （diastolic percentage） analysis of the artery of rats in each group showed that the endothelial dependent diastolic percentage of blood vascular ring of the HCY group and the SCQDC group in vitro was significantly decreased compared with that of the control group （P 〈 0.05, P 〈 0. 001 ）. Compared with the SCQDC group, the endothelial dependent diastolic percenuages of blood vascular ring in vitro of the Renshen group, the Shuangshen group and the Tongxinluo group were all increased in different degree. Conclusion： the result indicated that the symptims observed from the model rats established by combining methionine diet, basic diet, and weight loading swimming （such as listlessness, insensitive response, loss of weight, etc. ） conformed with the clinical patients with stagnancy of collateral-Qi in a deficiency condition, and the endothelial dysfunction was further exacerbated compared with the HCY group, after the intervention of different kinds of herbs to dredge collateral, the above symptoms could be improved in different degree, which proved that the endothelial dysfunction model with stagnancy of collateral-Qi .in a deficiency condition was established successfully.
出处
《山东中医药大学学报》
2008年第1期52-57,共6页
Journal of Shandong University of Traditional Chinese Medicine
基金
国家重点基础研究发展计划(国家973计划)项目(编号:2005CB523301)
关键词
络气虚滞
血管内皮功能障碍
动物模型
通络方药
stagnancy of collateral-Qi in a deficiency condition
endothelial dysfunction
animal model
herbs to dredge collateral
