Effect of AST-120 on Endothelial Dysfunction in Adenine-Induced Uremic Rats.
Effect of AST-120 on Endothelial Dysfunction in Adenine-Induced Uremic Rats.
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DOI：
10.1155/2014/164125
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发表时间：
2014
影响因子：
2.1
通讯作者：
Tomino Y
中科院分区：
文献类型：
--
作者：
Inami Y;Hamada C;Seto T;Hotta Y;Aruga S;Inuma J;Azuma K;Io H;Kaneko K;Watada H;Tomino Y
瞄准!慢性肾脏病（CKD）代表内皮功能障碍。单核细胞粘附被认为是动脉硬化的起始步骤。硫酸吲哚酚（IS）被认为是CKD动脉硬化的危险因素。口服吸附剂AST-120可延缓肾功能恶化，减少IS蓄积。本研究观察了腺嘌呤诱导的尿毒症大鼠单核细胞粘附及AST-120对粘附分子的影响。方法.将24只大鼠分为对照组、对照+AST-120组、腺嘌呤组和腺嘌呤+AST-120组。在第49天，通过对整个内皮表面进行成像来检查粘附于胸主动脉内皮的单核细胞的数量以及粘附和动脉粥样硬化相关分子的mRNA表达。检测人脐静脉内皮细胞ICAM-1和VCAM-1 mRNA的表达。结果腺嘌呤增加粘附单核细胞的数量，AST-120抑制这种增加。单核细胞粘附与血肌酐、IS有关。尿毒症大鼠动脉壁VCAM-1和TGF-β 1mRNA表达增加。IS诱导ICAM-1和VCAM-1mRNA表达增加。结论提示尿毒症可导致单核细胞粘附于动脉壁，AST-120可抑制单核细胞粘附随CKD进展而增加。
Aim. Chronic kidney disease (CKD) represents endothelial dysfunction. Monocyte adhesion is recognized as the initial step of arteriosclerosis. Indoxyl sulfate (IS) is considered to be a risk factor for arteriosclerosis in CKD. Oral adsorbent AST-120 retards deterioration of renal function, reducing accumulation of IS. In the present study, we determined the monocyte adhesion in the adenine-induced uremic rats in vivo and effects of AST-120 on the adhesion molecules. Methods. Twenty-four rats were divided into control, control+AST-120, adenine, and adenine+AST-120 groups. The number of monocytes adherent to the endothelium of thoracic aorta by imaging the entire endothelial surface and the mRNA expressions of adhesion and atherosclerosis-related molecules were examined on day 49. The mRNA expressions of ICAM-1 and VCAM-1 in human umbilical vein endothelial cells were also examined. Results. Adenine increased the number of adherent monocytes, and AST-120 suppressed the increase. The monocyte adhesion was related to serum creatinine and IS in sera. Overexpression of VCAM-1 and TGF-β1 mRNA in the arterial walls was observed in uremic rats. IS induced increase of the ICAM-1 and VCAM-1 mRNA expressions in vitro. Conclusion. It appears that uremic condition introduces the monocyte adhesion to arterial wall and AST-120 might inhibit increasing of the monocyte adherence with CKD progression.