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.
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)
