Renal tubular epithelial cell injury, apoptosis and inflammation are involved in melamine-related kidney stone formation
Renal tubular epithelial cell injury, apoptosis and inflammation are involved in melamine-related kidney stone formation
复制标题
肾小管上皮细胞损伤、凋亡和炎症参与三聚氰胺相关肾结石的形成
DOI：
10.1007/s00240-012-0507-x
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发表时间：
2012-12-01
影响因子：
--
通讯作者：
Xiao, Chunling
中科院分区：
文献类型：
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作者：
Lu, Xiuli;Gao, Bing;Xiao, Chunling
本研究的目的是了解三聚氰胺相关肾结石形成的发病机制。本文研究了三聚氰胺和三聚氰酸混合物对肾小管上皮细胞的影响。将雄性Sprague-Dawley大鼠分成两个实验组。治疗组每日喂饲含三聚氰胺和三聚氰酸的标准市售饲料，对照组喂饲普通饲料。用苏木精/伊红对大鼠肾脏标本进行染色，并使用偏光显微镜检查晶体。透射电镜观察肾小管上皮细胞。半定量RT-PCR检测单核细胞趋化蛋白-1（MCP-1）mRNA表达，MCP-1是一种对各种促炎刺激反应的蛋白质。采用原位末端标记法检测细胞凋亡。三聚氰胺相关晶体形成于肾小球和宽肾小管段，包括近曲肾小管、远曲肾小管、Henle肢袢和皮质和髓质的髓集合管。光镜下可见晶体导致肾小管管腔扩张，肾小管上皮细胞坏死。电镜下可见肾小管上皮细胞核轮廓不规则、浓缩，溶酶体相关结构增多，肾小管完整性缺失。皮质和髓质广泛可见凋亡细胞。三聚氰胺和三聚氰酸组MCP-1 mRNA表达显著增加。肾小管上皮细胞损伤、凋亡和炎症反应参与了三聚氰胺相关性肾结石的形成。本研究结果对于了解三聚氰胺相关性肾结石的发病机制及判断其临床预后具有重要意义。
The objective of this study is to understand pathogenesis of melamine-related kidney stone formation. We investigated the characterization of renal tubular cell under exposure to a mixture of melamine and cyanuric acid in vivo. Male Sprague-Dawley rats were separated into two experimental groups. Treatment group was administered daily with a standard commercial diet mixing with melamine and cyanuric acid, and control group was given a normal diet. Rat kidney specimens were stained with hematoxylin/eosin and the crystals were examined using a polarizing microscope. Renal tubular epithelial cells were observed by transmission electron microscopy. Semiquantitative RT-PCR assay was performed to determine monocyte chemoattractant protein-1 (MCP-1) mRNA expression, a protein in response to various proinflammatory stimuli. Apoptotic cells were examined by TUNEL assay. Melamine-associated crystals formed in glomerulus and wide renal tubule segment including proximal convoluted renal tubules, distal convoluted renal tubules, the limb loops of Henle and medullary collecting ducts in the cortex and medulla. Light microscopy results showed that the crystals lead to tubular lumen dilatation and tubular epithelial cell necrosis. It was observed that nucleus of renal tubular epithelial cells became irregular outlines and condensed, lysosomal-related structures increased, and integrity of renal tubule was deficient under electron microscopy. Apoptotic cells were noted widely in cortex and medulla. MCP-1 mRNA expression was significantly increased in the melamine and cyanuric acid-administrated group. Renal tubular epithelial cell injury, apoptosis and inflammation are involved in melamine-related kidney stone formation. Our findings are important for understanding pathogenesis of melamine-related kidney stone formation and estimating its clinical prognosis.