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| 替米沙坦激活PPARγ改善衰老大鼠脑血管内皮依赖性舒张功能 | |
| 引用本文： | 张黎黎,杨震,刘爱东,黄鸣清,周鹏,王沛坚.替米沙坦激活PPARγ改善衰老大鼠脑血管内皮依赖性舒张功能[J].成都医学院学报,2014,9(4):399-403. |
| 作者姓名： | 张黎黎 杨震 刘爱东 黄鸣清 周鹏 王沛坚 |
| 作者单位： | 1. 成都医学院第一附属医院神经内科,成都,610500 2. 成都医学院第一附属医院心血管内科,成都,610500 3. 福建中医药大学药学院,福州,350122 |
| 摘 要： | 目的观察替米沙坦对自然衰老模型大鼠脑血管内皮功能的改善作用及PPARγ与PPARβ阻断剂对上述作用的影响。方法选取12只雄性衰老SD大鼠（24月龄）,分衰老组（6只）和衰老-替米沙坦组（6只）（5mg/kg/d,灌胃给药,1月）,并以6月龄SD大鼠（6只）作为对照组。观察替米沙坦对大鼠血压、心率、脑血管功能的影响。分离大鼠脑基底动脉进行体外培养,以PPARβ的阻断剂GSK0660（1μM,24h）、PPARγ的阻断剂GW9662（1μM,24h）为工具药物,分析上述药物对替米沙坦（10μM,24h）介导的衰老大鼠模型脑血管内皮功能改善作用的影响。结果 24月龄衰老大鼠的血压、心率与6月龄大鼠比较,差异无统计学意义。与对照组大鼠比较,衰老模型大鼠乙酰胆碱诱导的脑血管内皮依赖性舒张功能显著下降,而硝酸甘油诱导的非内皮依赖性舒张功能未见明显改变。在培养血管组织中,替米沙坦孵育可显著改善衰老大鼠模型脑基底动脉的血管内皮依赖性舒张功能,PPARγ的阻断剂GW9662可显著阻断替米沙坦的作用,但PPARβ的阻断剂GSK0660对替米沙坦的作用则无显著影响。结论替米沙坦介导的脑血管内皮功能的改善作用依赖于PPARγ。 |
| 关 键 词： | 替米沙坦 过氧化物酶增殖物受体γ 血管内皮依赖性舒张功能 脑血管 衰老 |
Activation of PPAR Gamma by Telmisartan Improves Cerebrovascular Endothelium-Dependent Relaxation in Aging Rats |
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| Authors: | ZHANG Li-li YANG Zhen LIU Ai-dong HUANG Ming-qing ZHOU Peng WANG Pei-jian |
| Institution: | ZHANG Li-li , YANG Zhen , LIU Ai-dong , HUANG Ming-qing , ZHOU Peng , WANG Pei-jian (1. Department of Neurology, the First Affiliated Hospital, Chengdu Medical College, Chengdu 610500, China ; 2. Department of Cardiology,the First Affiliated Hospital ,Chengdu Medical College ,Chengdu 610500, China ; 3. College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China) |
| Abstract: | Objective To explore the effects of telmisartan on endothelium function in aging rats and the roles of PPARγand PPARβ.Methods Male twenty-four months old Sprague Dawley（SD）rats were used and were divided into aging group（n=6）,aging-telmisatran group（Aging-Telmi,n=6）.Male six-months old SD rats were used as control（Cont,n=6）.Rats in Aing-Telmi group were given telmisartan（5mg/kg/d）by gavage for one month,rats in aging group and Cont group were given saline as control.Blood pressure and heart rates were studied before and after treatment.Vasorelaxation of cerebrovascular were observed by wire myograph.Basilar arteries in rats were separated and cultured with DMEM.The effects of telmisartan（1μM,24h）on cultured aging basilar arteries were observed.PPAR gamma antagonist,GW9662（1μM,24h）and PPAR delta antagonist,GSK0660（1μM,24h）were also used respectively.Results Telmisartan administration did not affect the systolic blood pressure（SBP）and heart rate in aging rats.Impaired acetylcholine induced cerebraovascular endothelium dependent relaxation（EDR）but not nitroglycerin induced endothelium-independent relaxation was observed in aging rats.Telmisartan administration for a month improved the aging rat cerebrovascular EDR significantly but not endothelium-independent relaxation.In cultured basilar arteries,cultures with telmisartan improved the EDR significantly,but this effect was reversed by coculturedwith PPAR gamma antagonist,GW9662 but not PPAR delta antagonist,GSK 0660.Conclusion Telm-isartan improves aging rats cerebrovascular EDR in a PPAR gamma-dependent manner. |
| Keywords: | Telmisartan Peroxisome Proliferator-Activated Receptor Gamma Endothelium-Dependent Relaxation Cerebraovascular Aging |
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