Establishment of an inflamed animal model of diabetic nephropathy.
Establishment of an inflamed animal model of diabetic nephropathy.
复制标题
糖尿病肾病炎症动物模型的建立
DOI：
10.7150/ijbs.7875
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发表时间：
2014
影响因子：
9.2
通讯作者：
Liu BC
中科院分区：
文献类型：
--
作者：
Ma KL;Zhang Y;Liu J;Wu Y;Hu ZB;Ruan XZ;Liu BC
目的炎症应激在糖尿病肾病（DN）的发展中起着至关重要的作用。本研究旨在建立一种新型的DN炎症动物模型，并探讨其在DN中的意义。方法将非糖尿病db/m小鼠和糖尿病db/db小鼠随机分为db/m组、db/m+酪蛋白组、db/db组和db/db+酪蛋白组，持续8周。皮下注射酪蛋白诱导慢性炎症。每周测量体重和尿白蛋白/肌酐比（ACR）。采用酶联免疫吸附法测定血清淀粉样蛋白A （SAA）和肿瘤坏死因子-α (TNF-α)的血浆水平。病理染色、电镜观察肾脏病理形态及超微结构变化。采用免疫荧光染色和Western blotting检测肾脏足细胞特异性分子和炎性细胞因子的蛋白表达。结果与未注射酪蛋白的小鼠相比，注射酪蛋白的db/db小鼠肾脏ACR、血浆SAA和TNF-α水平、炎症因子蛋白表达、系膜扩张、胶原积累和足突消退均显著增加。酪蛋白注射可显著降低db/db小鼠肾脏特异性足细胞生物标志物Wilms' tumor-1和nephrin的表达，提示慢性炎症可加速db/db小鼠足细胞损伤。有趣的是，与db/m小鼠相比，注射酪蛋白的db/m小鼠没有发现明显的尿蛋白、炎症细胞因子表达或肾脏组织学变化。结论成功建立了DN的炎症动物模型，为探讨炎症应激下DN的发病机制提供了有益的工具。
Aims Inflammatory stress plays a crucial role in the progression of diabetic nephropathy (DN). This study aimed to establish a novel inflamed animal model of DN and to evaluate its significance in DN. Methods Nondiabetic db/m mice and diabetic db/db mice were randomly divided into four groups: db/m, db/m+casein, db/db, and db/db+casein for eight weeks. Casein was subcutaneously injected to induce chronic inflammation. Body weight and albumin to creatinine ratio (ACR) in the urine were measured every week. The plasma levels of serum amyloid protein A (SAA) and tumour necrotic factor-α (TNF-α) were determined with the enzyme-linked immunosorbent assay. The morphological changes to the renal pathology and ultra-microstructures were checked by pathological staining and electron microscopy. Immunofluorescent staining and Western blotting were used to determine the protein expression of podocyte-specific molecules and inflammatory cytokines in kidneys. Results ACR, plasma levels of SAA and TNF-α, protein expression of inflammatory cytokines, mesangial expansion, collagen accumulation, and foot process effacement in kidneys of casein-injected db/db mice were significantly increased compared with the db/db mice. Casein injection markedly decreased the protein expression of Wilms' tumor-1 and nephrin in kidneys of db/db mice, which are specific podocyte biomarkers, suggesting that chronic inflammation accelerates podocyte injuries in db/db mice. Interestingly, no obvious urinary protein, inflammatory cytokine expression, or histological changes in the kidneys of casein-injected db/m mice were found compared with the db/m mice. Conclusion An inflamed animal model of DN was successfully established and may provide a useful tool for investigating the pathogenesis of DN under inflammatory stress.
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影响因子：
16.2
作者：
Fröhlich, M;Imhof, A;Koenig, W
通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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通讯作者：
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影响因子：
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作者：
Nguyen DV;Shaw LC;Grant MB
通讯作者：
Grant MB
影响因子：
37.8
作者：
Festa, A;D'Agostino, R;Haffner, SM
通讯作者：
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