尿酸通过诱导线粒体钙稳态失衡介导内皮细胞炎症反应  

Mitochondrial calcium homeostasis imbalance was associated with uric acid induced endothelial inflammation

作　　者：齐卡[1] 冯哲[1] 洪权[1] 傅博[1] 崔少远[1] 陈香美[1] 吴镝[1] 

机构地区：[1]中国人民解放军总医院,北京100853

出　　处：《山东医药》2010年第20期15-18,共4页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(30670983);国家重点基础研究发展规划"973"项目(2007CB507400)

摘　　要：目的探讨线粒体钙稳态失衡在高尿酸(UA)导致的血管内皮细胞炎症中的病理生理机制。方法采用Fluo-3 AM及Rhod-2 AM分别对UA刺激后的人脐静脉内皮细胞(HUVEC-C)进行胞质钙离子浓度([Ca2+]i)和线粒体钙离子浓度([Ca2+]mito)的特异性染色;RT-PCR法检测其C反应蛋白(CRP)和细胞间黏附分子1(ICAM-1)的mRNA表达变化;Western blot检测ICAM-1的蛋白变化;ELISA法检测其培养液上清白细胞介素6(IL-6)的释放变化情况。结果HUVEC-C经600μmol/L的UA刺激后,其[Ca2+]i未见明显变化,而[Ca2+]mito呈波浪式升高(P<0.05),并在24 h内保持较高的状态;CRP、ICAM-1、IL-6均在UA刺激后升高(P<0.05)。结论UA可导致内皮细胞炎症反应,[Ca2+]mito的升高与之相关,提示线粒体钙稳态失衡在UA导致的内皮炎症反应中起一定的介导作用。Objective To evaluate the characteristics and mechanism of mitochondrial calcium homeostasis imbalance in vascular endothelial cells inflammation induced by uric acid.Methods Fluo-3 AM and Rhod-2 AM were employed to measure the introcellular calcium concentration（i） and mitochondrial calcium concentration（mito） of human umbilical vein endothelial cells（HUVEC-C） after stimulation of UA,respectively.RT-PCR was used to detected C-reactive protein（CRP） and the intercellular adhesion molecule-1（ICAM-1） levels of mRNA expression.Western blot was used to detect the ICAM-1 protein levels and ELISA was used to detect the culture medium on the innocence interleukin-6（IL-6） changes.Results After stimulation of 600 μmol/L of UA,the i of HUVEC-C was not changed significantly;however,the mito increased rapidly in a conk manner（P0.05） and it maintained as a relative high state in 24 hours.CRP,ICAM-1 and IL-6 were significantly increased after stimulation of UA（P0.05）.Conclusion Uric acid can lead to endothelial cell inflammatory response,which may be related to the increasing of mito in HUVEC-C.Mitochondrial calcium homeostasis imbalance was involved in endothelial inflammatory response induced by uric acid.

关 键 词：尿酸 线粒体 钙 内皮细胞 炎症 

分 类 号：R364.5[医药卫生—病理学]