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《环球中医药》[ISSN:1006-6977/CN:61-1281/TN]

卷:

第9卷

期数:

2016年08期

页码:

918-923

栏目:

论著

出版日期:

2016-08-06

文章信息/Info

Title:

Effects of Lishi Huoxue prescription on NO, ET-1 and the influence of related gene expression in the rat with hyperuricemia

作者:

王淳 张建军 郑媛 刘畅 瞿研 王林元

100029 北京中医药大学基础医学院(王淳、张建军、刘畅),中药学院(瞿研、王林元); 西安红会医院药房(郑媛)

Author(s):

WANG Chun;  ZHANG Jian-jun;  ZHENG Yuan;  et al.

Beijing University of Chinese Medicine, Beijing 100029, China

关键词:

高尿酸血症;  一氧化氮;  血清内皮素;  eNOS mRNA;  ET-1 mRNA;  利湿活血方

Keywords:

Hyperuricemia;  Nitric oxide;  Endothelin-1;  Endothelial nitric oxide synthase mRNA;  Endothelin-1 mRNA;  Lishi Huoxue prescription

分类号:

R285.5

DOI:

10.3969/j.issn.1674-1749.2016.08.004

文献标志码:

A

摘要:

目的 探讨中药利湿活血方对高尿酸血症模型大鼠血管内皮功能的保护作用及其机制。方法 将70只雄性SD大鼠随机分成空白组、模型组、苯溴马隆(阳性药)组、四妙丸组、利湿活血方组、拆方Ⅰ组、拆方Ⅱ组,共7组,每组10只。除空白组外,其余各组均以酵母膏、腺嘌呤连续灌胃14天,制备高尿酸血症模型。验模后,各给药组灌胃给予相应药物,空白组和模型组给予等体积蒸馏水,连续14天。末次给药后,测定各组大鼠血清一氧化氮(nitric oxide,NO)、内皮素-1(endothelin-1,ET-1)的含量,实时荧光定量PCR检测肾组织内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)mRNA、ET-1 mRNA表达水平,制作主动脉病理切片,光镜下观察主动脉超微病理学的改变。结果 模型组大鼠血清尿酸(uric acid,UA)、ET-1含量升高,NO含量降低,与空白组比较,差异有统计学意义(P＜0.05); 阳性药(苯溴马隆)组、四妙丸组、利湿活血方组、拆方Ⅰ组大鼠血清UA和ET-1含量明显降低,与模型组比较,差异有统计学意义(P＜0.05); 苯溴马隆组、四妙丸组、利湿活血方组、拆方Ⅰ组、拆方Ⅱ组实验动物血清NO含量均明显高于模型组(P＜0.05)。模型组大鼠肾组织ET-1 mRNA表达水平和空白组相比显著升高(P＜0.05); 苯溴马隆组、利湿活血方组大鼠肾组织ET-1 mRNA表达水平与模型组相比显著降低(P＜0.05),利湿活血方组与四妙丸组、拆方Ⅰ组、拆方Ⅱ组比较,ET-1 mRNA表达水平明显降低(P＜0.05)。模型组大鼠肾组织eNOS mRNA表达水平和空白组相比,显著降低(P＜0.05); 苯溴马隆组、利湿活血方组大鼠肾组织eNOS mRNA表达水平与模型组相比显著升高(P＜0.05)。主动脉病理变化以模型组损伤最为明显,各给药组均有不同程度的改善,以苯溴马隆组及利湿活血方组的改善最为明显。结论 中药利湿活血方从湿热壅盛、瘀血阻滞的病机出发,以清热利湿、化瘀散结为治法,在降低高尿酸血症大鼠血清尿酸的同时,减轻组织炎性反应,保护血管内皮舒缩功能,发挥综合作用,达到较好的治疗效果。其作用机制可能与下调ET-1 mRNA表达、上调eNOS mRNA表达有关。

Abstract:

Objective To explore the endothelial protection and mechanism of Chinese medicine Lishi Huoxue prescription(LSHXF)in the rat model of hyperuricemia.Methods Male SD rats were randomly divided into 7 groups: normal group, model group, benzbromarone group, simiaowan group, Lishi Huoxue prescription group, decomposed recipes Ⅰ group and decomposed recipes Ⅱ group. Hyperuricemia rat model was established by yeast and high purine two weeks. If the rat model was successful, the appropriate drugs administered to the rats of the administration group, the normal group and model group were given distilled water volume, for 14 days. After the last time of administration, the content of NO and ET-1 in serum were detected by radiommunoassay, real time fluorescence quantitative PCR detection was used to detect the expression level of renal tissue eNOS mRNA and ET-1 mRNA. The change of aorta ultrastructural pathology was observed. Results Compared with the normal group, the content of UA and ET-1 in model group was increased, the NO content was decreased, the results had significant difference(P＜0.05); compared with model group, the level of UA and ET-1 in Benzbromarone group, Simiaowan group, Lishi Huoxue prescription group, decomposed recipes Ⅰ group were obviously reduced, the results had significant difference(P＜0.05); the content of NO in benzbromarone group, Simiaowan group, Lishi Huoxue prescription group, decomposed recipes Ⅰ group, decomposed recipes Ⅱ group was obviously higher than that in model group, the difference was statistically significant(P＜0.05); compared with the normal group, the level of ET-1 mRNA and eNOS mRNA of model group were significant differences(P＜0.05), there were significant difference(P＜0.05)between Lishi Huoxue prescription group and model group on level of ET-1 mRNA and eNOSmRNA. Lishi Huoxue prescription group compared with decomposed recipes Ⅰ and Ⅱ group, the expression of ET-1 mRNA of Simiaowan group was significantly reduced, the result had significant difference(P＜0.05). Compared with the mode group, the expression of eNOS mRNA of Lishi Huoxue prescription group was obviously increased, the result had significant difference (P＜0.05). The most obvious pathological changes of aortic injury were in model group, there were different degrees of improvement in each dose groups, benzbromarone group and Lishi Huoxue prescription group improved the most obvious. Conclusions The Chinese herbal compounds of Lishi Huoxue prescription which is based on dampness-heat and blood stasis. The treatment is clearing away heat and promoting blood circulation. The medicine can reduce the serum uric acid of the hyperuricemia rats, reduce the inflammatory response, and protect vascular endothelial function, achieve the better therapeutic effect. The mechanism may be related to down-regulated the expression of ET-1 mRNA, up-regulated the expression of eNOS mRNA.

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备注/Memo

备注/Memo:

基金项目: 国家自然科学基金(81273632)
作者简介: 王淳(1970- ),博士,副教授,硕士生导师。研究方向:中医药防治高尿酸血症和痛风。E-mail:chunwang_2008@163.com
通讯作者:王林元(1961- ),博士,副教授,硕士生导师。研究方向:中药新技术新制剂研究与应用。E-mail: wangly@bucm.edu.cn

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更新日期/Last Update: 2016-08-06