桃核承气改良方对兔血管内膜剥脱术后内皮素和一氧化氮及一氧化氮合酶的影响

Effects of improved prescription of Taoren Chengqi decoction on endothelin, nitric oxide and nitricoxide synthase after balloon angioplasty

背景：大量的研究结果已证实，内皮细胞如能够早期覆盖受损的血管内膜层，则可避免血管内再狭窄的发生。目的：通过与西药作用对比，观察中药桃核承气改良方对兔血管损伤后内皮细胞生长及功能的影响。设计、时间及地点：随机对照动物实验，于2007—04／11在辽宁中医药大学和中国医科大学完成。材料：健康新西兰大耳白兔40只，体质量2．0～2．5kg，高酯饲料喂养4周行腹主动脉内膜剥脱造模，制备动脉粥样硬化模型。桃核承气改良方为辽宁中医药大学附属第一医院制剂产品；舒降之为杭州默沙东制药有限公司产品；阿司匹林为拜尔药业集团有限公司产品。方法：40只兔随机数字表法分为4组。造模后模型组、中药组、西药组正常饲料喂养，中药组予桃核承气改良方13．5mL／kg灌胃4周，西药组予舒降之、阿司匹林混合液13．5mL／kg灌胃4周，模型组、空白组予生理盐水13．5mL／kg灌胃4周。主要观察指标：①造模后1，28d采用硝酸还原法法和比色法测定血浆内皮素1、血清一氧化氮含量。②免疫组织化学法测定血管中内皮素1、内皮型一氧化氮合酶蛋白表达。结果：32只新西兰大耳白兔进入结果分析，模型组（n=8）、中药组（n=10）、两药组（n=8）和空白组（n=6）。①与空白组相比，其他3组造模后1d血浆内皮素1升高，血清一氧化氮含量下降（P〈0．05）。造模后28d兔中药组、西药组血浆内皮素1较模型组明显降低，血清一氧化氮明显升高（P〈0．05）。②血管中内皮素1表达模型组明显高于其他3组（P〈0．05）；中药组、西药组较模型组显著减弱（P〈0．05）。模型组内皮型一氧化氮合酶表达明显低于其他3组（P〈0．05）；中药组、西药组较模型组显著增强（P〈0．05）。结论：桃核承气改良方能够促进内皮素与一氧化氮之间的平衡协调，有利于血管内皮细胞的修复。

BACKGROUND： Plenty of studies have demonstrated that early growth of endothelial cells to injured tunica intima can prevent intravascular restenosis. OJECTIVE： To investigate the effects of improved prescription of Taoren Chengqi decoction （Peach Kernel decoction for strengthening qi） on the growth and activation of endothelial cells in rabbits after balloon angioplasty. DESIGN, TIME AND SETTING： Randomized controlled animal trial was performed at the Liaoning University of Traditional Chinese Medicine and China Medical University from April to November 2007. MATERIALS： Forty healthy New Zealand White Rabbits weighing 2.0-2.5 kg were fed with high fat diet for 4 weeks, and created models of artherosclerosis by stripping abdominal aortic tunica intima. The improved prescription of Taoren Chengqi decoction was product of the First Hospital of Liaoning University of Traditional Chinese Medicine; Zocor （simvastatin） is product of Hangzhou Moshadong Pharmaceutical Co., Ltd., Zhejiang Province; aspirin was product of Bayer. METHODS： Forty rabbits were randomly divided into model group （n=11）, Chinese medicine group （n=12）, western medicine group （n=11 ）, and blank group （n=6）. After modeling, the model group, Chinese medicine group, western medicine group were fed with normal diet. Additionally, the Chinese medicine group was intragastrically infused improved prescription of Taoren Chengqi decoction （13.5 mL/kg） for 4 weeks; the western medicine group was infused with simvastatin and aspirin mixture （13.5 mL/kg） for 4 weeks; the model group and blank group were infused with normal saline （13.5 mL/kg） for 4 weeks. MAIN OUTCOME MEASURES： The levels of plasma endothelin-1 （ET-1） and serum nitric oxide （NO） were measured by radio-immunity and colorimetry; vascular ET-1 and nitricoxide synthase （NOS） protein expressions were determined using immunohistochemical method. RESULTS： Thirty-two rabbits were included in the final analysis. Compared with the blank group, the plasma ET-1 was significantly increased and serum NO was significantly decreased in the other groups one day after modeling （P 〈 0.05）. The plasma ET-1 was significantly decreased but serum NO was significantly increased in the Chinese medicine group and western medicine group 28 days after modeling （P 〈 0.05）. The expression level of vascular ET-1 was significantly higher than the other groups （P 〈 0.05）; the expression level of vascular ET-1 significantly decreased in the Chinese medicine group and western medicine group （P 〈 0.05）. NOS expression in the model group was significantly lower than the other groups （P 〈 0.05）, and NOS significantly increased in the Chinese medicine group and western medicine group （P 〈 0.05）. CONCLUSION： The improved prescription of Taoren Chengqi decoction can improve endothelin and NO balance in serum and injured vessels, and aid normal growth of vascular endothelial cells.