氯沙坦对兔高尿酸血症介导的动脉粥样硬化的影响

注册本刊作者	作者投稿查稿
专家远程审稿	编辑在线审稿
编务办公专区	主编办公专区

下载文档

工作动态

联系方式

发行周期:: 月刊

主管单位:: 上海市卫生健康委员会

主办单位:: 上海市医学会

编辑出版:: 《上海医学》编辑部

联系地址:: 上海市北京西路1623号

邮编:: 200040

电话:: 021-62178606

传真:: 021-62178606

邮箱:: smasmj@shsma.org.cn

ISSN:: ISSN0253-9934

CN:: CN31-1366/R

收款账号:: 1001255309008900719

账户名:: 上海市医学会

开户行:: 工商银行上海市静安寺支行

友情链接

上海市医学会

当前位置：首页 > 过刊浏览->2012年第12期

氯沙坦对兔高尿酸血症介导的动脉粥样硬化的影响
Effects of losartan on uric acid-induced atherosclerosis in rabbits

浏览(3441) 下载(0)

DOI:

作者:: 郑宏超,李宁,丁耀有,缪培智,管思斌,顾水明
ZHENG Hong-chao，Li Ning，DING Yao-you，Miao Pei-zhi，

作者单位:: 上海徐汇区中心医院
Central hospital of Xuhui District, Shanghai

关键词:: 高尿酸血症；动脉粥样硬化；氯沙坦；血管平滑肌细胞；免疫组织化学染色；透射电镜； LDLR
Hyperuricemia； Atherosclerosis； Losartan； Vascular smooth muscle cells(VSMCs)； Immunohistochemistry；Transmission electron microscope；LDLR

摘要:: 目的：观察高尿酸血症对兔动脉粥样硬化（AS）形成的影响及应用氯沙坦后的保护作用。方法：雄性新西兰大白兔基础喂养一周后，随机接受12周普通饲料（对照组；n=12）、高嘌呤饲料（高尿酸组；n=12）、高脂+高嘌呤饲料（高脂+尿酸组；n=12）和高嘌呤饲料+氯沙坦30 mg/ ( kg•d)（氯沙坦组；n=12）的喂养。12周处死动物，取主动脉，应用免疫组化方法测定血管平滑肌细胞PCNA蛋白表达，透射电镜观察粒体结构改变，PCR法检测低密度脂蛋白受体（LDLR)mRNA变化，Western blot方法检测LDLR蛋白表达。分组和处死动物前测定血尿酸。结果：高尿酸组血清尿酸水平及血管平滑肌细胞PCNA蛋白表达显著高于对照组[(85.23 ±7.02) μmol/L比（52.26 ±5.42）μmol/L，P＜0.01；(28.35±1.61)%比(9.60±1.61)%，P＜0.01]，LDLR mRNA及蛋白表达较对照组明显减低（P＜0.05），线立体结构损伤。这些改变在高脂+尿酸组更加严重。氯沙坦组血清尿酸浓度和血管平滑肌细胞PCNA蛋白表达比高尿酸组显著降低[（56.83 ±5.34）μmol/L比(85.23 ±7.02)μmol/L，P＜0.01；(16.53±3.22)% 比(28.35±1.61)%，P＜0.01]，LDLR mRNA及蛋白表达较高尿酸组明显升高（P＜0.05），且线粒体结构完整性得到保护。结论：高尿酸血症对血管平滑肌细胞及LDLR表达产生不良作用并损伤线粒体促使动脉粥样硬化的形成。氯沙坦可有效阻抑上述变化，抑制高尿酸血症介导的动脉粥样硬化形成。
Objective： To evaluate the role of uric acid (UA) in atherosclerosis formation in rabbits and the beneficial effects of losartan. Methods ： Forty-eight male New Zealand white rabbits were randomly divided into four groups: control group (common diet), UA group (high purine diet), UA+ hypercholesterolemia group (high UA and cholesterol diet), and losartan group (high purine diet + losartan 30 mg/ kg•d). All animals were killed after 12 weeks. Serum UA was measured, and mitochondrial structure, and expression of vascular smooth muscle cell PCNA were examined. The transcriptional changes of low-density lipoprotein receptor(LDLR) was evaluated with PCR and Western blot. Results: The level of uric acid and expression of PCNA in model group was significantly higher than in control group[(85.23 ±7.02) μmol/L　ｖｓ．（52.26 ±5.42）μmol/L，P＜0.01；(28.35±1.61)%　ｖｓ． (9.60±1.61)%，P＜0.01]; The transcription and expression of LDLR were significantly reduced (all P＜0.05 vs. control group) in model group.The level of uric acid and expression of PCNA were significantly reduced in losartan group compared with those in model group[（56.83 ±5.34）μmol/L　ｖｓ．(85.23 ±7.02)μmol/L，P＜0.01；(16.53±3.22)% 　ｖｓ．(28.35±1.61)%，P＜0.01]. The transcription and expression of LDLR were significantly higher (all P＜0.05 vs. model group) in losartan group.Losartan also preserved the function and structure of mitochondria . Conclusion：Uric acid induces atherosclerosis by increasing proliferation of vascular smooth muscle cells, down-regulating LDLR mRNA transcription and protein translation, damaging mitochondrial structure. Losartan may have a beneficial effect on the prevention of hyperuricemia-induced atherogenesis.

主管单位：上海市卫生健康委员会主办单位：上海市医学会
©2025《上海医学》编辑部沪ICP备09078599号
您是本站第29224008名访问者
网站管理