替米沙坦对人血管内皮细胞炎性反应的影响及其相关机制被引量：4

The effect of telmisartan on inflammation of human vascular endothelial cells and the related mechanism

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摘要目的探讨替米沙坦对晚期糖基化终末产物(AGEs)诱导人脐静脉内皮细胞(HUVECs)炎性反应的影响及与过氧化物酶体增殖物激活受体γ(PPARγ)的关系。方法酶消化法获取HUVECs。实验分8组:BSA组;AGEs组;以不同浓度替米沙坦刺激细胞30 min,再加AGEs,依次为TM 1组(1 nmol/L)、TM 2组(10 nmol/L)、TM 3组(100 nmol/L)、TM 4组(1000 nmol/L);GW9662组:GW9662预先刺激细胞30 min后,加替米沙坦和AGEs;15d-PGJ_2组:15d-PGJ_2预先刺激细胞30 min后,加AGEs。各组均刺激细胞24 h。采用RT-PCR法检测PPARγ、AGEs受体(RAGE)和单核细胞趋化蛋白1(MCP-1)mRNA的表达;荧光探针2,7-二氯二氢荧光素乙酰乙酸检测细胞内活性氧的变化。结果替米沙坦呈浓度依赖性抑制AGEs诱导的MCP-1 mRNA表达。与AGEs组比较,TM 4组和15d-PGJ_2组PPARγ mRNA水平明显升高,RAGE mRNA和MCP-1 mRNA水平明显下降,活性氧荧光信号强度明显减弱。与TM 4组比较,GW9662组PPARγ mRNA的表达水平明显下降,RAGE mRNA和MCP-1 mRNA的表达水平明显升高,活性氧荧光信号强度明显增强。结论替米沙坦可抑制AGEs诱导的HUVECs炎性反应;替米沙坦可能通过激活PPARγ抑制HUVECs炎性反应。 Objective To observe the effect of telmisartan on advanced glycation end products （AGEs）-induced formation of reactive oxygen species（ROS） and expression of monocyte chemoattractant protein-1（MCP-1） and the relation with PPARγ in HUVECs. Methods Gene expression of PPART,AGE receptor（RAGE） and MCP-1 was analysed by semiquantitative reverse transcription-polymerase chain reaction（RT-PCR） method. Intracellular formation of ROS was measured using the fluorescent probe DCFH-DA. Results Telmisartan downregulated MCP-1 mRNA levels induced by AGEs in a dose-dependent manner. Furthermore, telmisartan 4 group （1000 nmol/L） and 15d-PGJ2 group produced higher level of expression of PPARγ mRNA than AGEs group did,but produced lower level of expression of RAGE mRNA,MCP-1 mRNA and inhibited intracellular ROS generation. Compared with telmisartan 4 group, GW9662 group produced lower level of expression of PPARγ mRNA, but higher level of expression of RAGE mRNA,MCP-1 mRNA and promoted intracellular ROS generation. Conclusion The results indicate that telmisartan can inhibit inflammatory reaction of HUVECs induced by AGE＇s via PPARγ activation.

作者郑晓新徐尚华谢良地许昌声陶硕秋

机构地区福建医科大学教学医院南平市第一医院心内科福建医科大学附属第一医院高血压研究所

出处《中华老年心脑血管病杂志》 CAS 北大核心 2010年第9期833-836,共4页 Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基金福建省科技厅资助项目(2007F3129)

关键词糖基化终产物高级过氧化物酶体增殖物激活受体趋化因子CCL2 脐静脉内皮细胞 glycosylation end products, advanced peroxisome proliferator-activated receptors chemokine CCL2 umbilical veins endothelial cells

分类号 R965 [医药卫生—药理学]

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