Indoxyl sulphate promotes aortic calcification with expression of osteoblast-specific proteins in hypertensive rats
Indoxyl sulphate promotes aortic calcification with expression of osteoblast-specific proteins in hypertensive rats
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DOI：
10.1093/ndt/gfm861
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发表时间：
2008-06-01
影响因子：
6.1
通讯作者：
Niwa, Toshimitsu
中科院分区：
文献类型：
--
作者：
Adijiang, Ayinuer;Goto, Sumie;Niwa, Toshimitsu
背景。5期慢性肾脏疾病（CKD）与主动脉钙化增强相关。本研究的目的是确定是否给药吲哚酚硫酸盐（IS），一种尿毒症毒素，刺激主动脉钙化的进展。大鼠组包括：(i)达尔盐耐药正常大鼠（DR），摄入0.3%的盐；（ii）达尔盐敏感高血压大鼠（DS），摄入2.0%的盐；（iii）达尔盐敏感高血压大鼠（DS-IS），摄入2.0%的盐和200 mg/kg的IS水。30周后，切除大鼠主动脉组织和肾脏组织进行组织学和免疫组化分析。von Kossa染色在DS- is大鼠弓主动脉均可见严重血管钙化，而DS和DR大鼠均未见严重血管钙化。免疫组化结果显示，DS-IS大鼠主动脉钙化区包埋细胞中存在骨桥蛋白、核心结合因子1 （Cbfal）、碱性磷酸酶（ALP）、骨钙蛋白、IS和有机阴离子转运蛋白（OAT） 3共定位。DS- is大鼠弓形主动脉、胸主动脉和腹主动脉壁厚较DS和DR大鼠明显增加。DS- is大鼠肾小球肥大程度、系膜扩张程度、马氏三色阳性小管间质面积及转化生长因子ss1在肾小球和小管间质的表达均明显高于DS和DR大鼠。IS通过表达成骨细胞特异性蛋白和主动脉壁增厚诱导主动脉钙化。IS不仅是一种肾毒素，也是一种血管毒素，可能促进5期CKD患者主动脉钙化的进展。
Background. Stage 5 chronic kidney disease (CKD) is associated with enhanced aortic calcification. The aim of this study was to determine if the administration of indoxyl sulphate (IS), a uraemic toxin, stimulates the progression of aortic calcification.Methods. The rat groups consisted of (i) Dahl salt-resistant normotensive rats (DR) with intake of 0.3% salt, (ii) Dahl salt-sensitive hypertensive rats (DS) with intake of 2.0% salt and (iii) Dahl salt-sensitive hypertensive IS-administered rats (DS-IS) with intake of 2.0% salt and 200 mg/kg of IS in water. After 30 weeks, their aortic and kidney tissues were excised for histological and immunohistochemical analyses.Results. Severe vascular calcification was observed by von Kossa staining in the arcuate aorta of all the DS-IS rats, but hardly in DS or DR rats. Immunohistochemistry demonstrated that osteopontin, core binding factor 1 (Cbfal), alkaline phosphatase (ALP), osteocalcin, IS and organic anion transporter (OAT) 3 were colocalized in the cells embedded in the aortic calcification area of DS-IS rats. Wall thickness was significantly increased in arcuate, thoracic and abdominal aortas of DS-IS rats compared with DS and DR rats. DS-IS rats showed significantly increased extent of glomerular hypertrophy, mesangial expansion, Masson's trichrome-positive tubulointerstitial area and glomerular and tubulointerstitial expression of transforming growth factor-ss l as compared with DS and DR rats.Conclusions. IS induced aortic calcification with expression of osteoblast-specific proteins and aortic wall thickening. IS is not only a nephrotoxin but also a vascular toxin, and may contribute to the progression of aortic calcification in stage 5 CKD patients.