Vascular, valvular and kidney calcification manifested in mouse models of adenine-induced chronic kidney disease.
Vascular, valvular and kidney calcification manifested in mouse models of adenine-induced chronic kidney disease.
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DOI：
10.1080/0886022x.2023.2228920
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发表时间：
2023-12
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3
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慢性肾脏病（CKD）患者异位钙化（EC）累及多个器官系统。以前的CKD动物模型主要集中在某种组织学异常，但没有显示出与各种组织中钙化发展的相关性。本研究比较了小鼠CKD进展期间各种组织中的钙化沉积。将8周龄雄性C57 BL/6 J小鼠随机分为7组：基础、腺嘌呤、高磷、腺嘌呤和高磷饮食，持续12-16周（分别为Ct 116、A12、P16或AP 16）;腺嘌呤饮食4-6周;饲喂高磷或腺嘌呤和高磷日粮10-12周（分别为A6 + P10、A4 + P12或A4 + AP 12）。与Ct 116小鼠相比，P16小鼠仅表现出轻微的血清钙和磷异常，A12小鼠的肾损害最严重，A4 + P12和A6 + P10小鼠的CKD、矿物质异常以及肾脏和主动脉瓣的轻度钙化情况相似; A4 + AP 12和AP 16组有严重的肾损害，肾、主动脉瓣和动脉瘤中的矿物质异常和钙化。此外，钙磷酸盐颗粒不仅沉积在肾小管间质室，但在肾小球和肾小管基底膜。EC在各种组织的元素组成相匹配的人类心血管组织的钙化能量色散光谱测定。随着矿物质代谢紊乱和EC的进展，CKD的严重程度是无与伦比的。钙化在不同组织中密切相关，并在肾小球和肾小管基底膜中观察到。以前的CKD动物模型主要集中在某种组织学异常，但缺乏对EC在各种组织中相互作用的研究。本研究比较了小鼠CKD进展期间几种组织中的钙化沉积，这是密切相关的。CKD的严重程度与异位钙化的发展是无与伦比的。在CKD小鼠中检测到肾小球和肾小管基底膜钙化，这在临床上被认为是极其罕见的。
Ectopic calcification (EC) involves multiple organ systems in chronic kidney disease (CKD). Previous CKD-animal models primarily focused on a certain histological abnormality but did not show the correlation with calcified development among various tissues. This study compared calcified deposition in various tissues during CKD progression in mice. Male 8-week-old C57BL/6J mice were randomly allocated to the seven groups: a basic, adenine, high-phosphorus, or adenine and high-phosphorus diet for 12–16 weeks (Ctl16, A12, P16, or AP16, respectively); an adenine diet for 4–6 weeks; and a high-phosphorus or adenine and high-phosphorus diet for 10–12 weeks (A6 + P10, A4 + P12, or A4 + AP12, respectively). Compared to the Ctl16 mice, the P16 mice only displayed a slight abnormality in serum calcium and phosphorus; the A12 mice had the most serious kidney impairment; the A4 + P12 and A6 + P10 mice had similar conditions of CKD, mineral abnormalities, and mild calcification in the kidney and aortic valves; the A4 + AP12 and AP16 groups had severe kidney impairment, mineral abnormalities and calcification in the kidneys, aortic valves and aortas. Furthermore, calcium-phosphate particles were deposited not only in the tubulointerstitial compartment but in the glomerular and tubular basement membrane. The elemental composition of EC in various tissues matched the calcification of human cardiovascular tissue as determined by energy dispersive spectroscopy. The severity of CKD was unparalleled with the progression of mineral metabolism disorder and EC. Calcification was closely related in different tissues and observed in the glomerular and tubular basement membranes. Previous CKD-animal models primarily focused on a certain histological abnormality but lacked investigations of the interplay of EC in various tissues. This study compared calcified deposition in several tissues during CKD progression in mice, which was closely related. The severity of CKD was unparalleled with the development of ectopic calcification. Glomerular and tubular basement membrane calcification was detected in CKD mice, which has been considered extremely rare in clinical.