Adijiang Ayinuer, Goto Sumie, Uramoto Satsuki, Nishijima Fuyuhiko, Niwa Toshimitsu
Department of Clinical Preventive Medicine, Nagoya University Hospital, Nagoya, Japan.
Nephrol Dial Transplant. 2008 Jun;23(6):1892-901. doi: 10.1093/ndt/gfm861. Epub 2008 Mar 11.
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.
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.
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-ssl as compared with DS and DR rats.
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.
5期慢性肾脏病（CKD）与主动脉钙化增强有关。本研究的目的是确定尿毒症毒素硫酸吲哚酚（IS）的给药是否会刺激主动脉钙化的进展。
大鼠分组包括：（i）摄入0.3%盐的Dahl盐抵抗正常血压大鼠（DR）；（ii）摄入2.0%盐的Dahl盐敏感高血压大鼠（DS）；（iii）摄入2.0%盐且饮水中含200mg/kg IS的Dahl盐敏感高血压IS给药大鼠（DS-IS）。30周后，切除它们的主动脉和肾脏组织进行组织学和免疫组织化学分析。
通过冯·科萨染色在所有DS-IS大鼠的弓状主动脉中观察到严重的血管钙化，但在DS或DR大鼠中几乎未观察到。免疫组织化学显示，骨桥蛋白、核心结合因子1（Cbfal）、碱性磷酸酶（ALP）、骨钙素、IS和有机阴离子转运体（OAT）3在DS-IS大鼠主动脉钙化区域内的细胞中共定位。与DS和DR大鼠相比，DS-IS大鼠的弓状、胸段和腹段主动脉壁厚度显著增加。与DS和DR大鼠相比，DS-IS大鼠的肾小球肥大、系膜扩张、Masson三色染色阳性的肾小管间质面积以及转化生长因子-β1在肾小球和肾小管间质中的表达程度均显著增加。
IS诱导主动脉钙化并伴有成骨细胞特异性蛋白表达和主动脉壁增厚。IS不仅是一种肾毒素，也是一种血管毒素，可能促使5期CKD患者主动脉钙化的进展。
