Establishment of an experimental rat model of tacrolimus-induced kidney injury accompanied by interstitial fibrosis
Establishment of an experimental rat model of tacrolimus-induced kidney injury accompanied by interstitial fibrosis
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DOI：
10.1016/j.toxlet.2021.01.020
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发表时间：
2021-02-05
影响因子：
3.5
通讯作者：
Masuda, Satohiro
中科院分区：
文献类型：
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作者：
Fu, Rao;Tajima, Soichiro;Masuda, Satohiro
肾毒性是他克莫司的主要不良反应，然而，其潜在机制仍有待充分阐明。虽然已经报道了几种他克莫司诱导的肾毒性动物模型，但大多数肾损伤大鼠模型含有他克莫司以外的因素。在这里，我们报告了一个新的肾毒性与间质纤维化大鼠模型的发展，他克莫司管理诱导。30只Wistar大鼠随机分为假手术组（Sham）、缺血再灌注损伤组（IRI）、他克莫司治疗组（TAC）和他克莫司治疗I/R损伤组（TAC + IRI）。IR损伤大鼠经他克莫司治疗2周后，血清肌酐（Scr）、尿素氮（BUN）、血清镁（Mg）和血清钾（K）升高，提示肾功能下降。此外，他克莫司治疗联合IR损伤增加了组织学损伤（肾小管空泡化、肾小球硬化和间质纤维化）以及肾皮质中的α-平滑肌肌动蛋白（α-SMA）、转化生长因子-β（TGF-β）和肾损伤分子-1（KIM-1）表达。总之，我们通过在缺血-再灌注后通过他克莫司给药建立模拟肾移植的条件，在2周内建立了他克莫司诱导的肾损伤大鼠模型，伴有间质纤维化。(C)2021爱思唯尔有限公司版权所有。
Nephrotoxicity is the major adverse reaction to tacrolimus; however, the underlying mechanisms remain to be fully elucidated. Although several tacrolimus-induced nephrotoxicity animal models have been reported, most renal injury rat models contain factors other than tacrolimus. Here, we report the development of a new nephrotoxicity with interstitial fibrosis rat model induced by tacrolimus administration. Thirty Wistar rats were randomly divided into four groups: sham-operated (Sham), vehicle-treated ischemia reperfusion (UR) injury (IRI), tacrolimus treated (TAC) and tacrolimus treated I/R injury (TAC + IRI). Rats subjected to IR injury and treated with tacrolimus for 2 weeks showed higher serum creatinine (Scr), blood urea nitrogen (BUN), serum magnesium (Mg) and serum potassium (K), indicating decreased renal function. In addition, tacrolimus treatment combined with IR injury increased histological injury (tubular vacuolation, glomerulosclerosis and interstitial fibrosis), as well as alpha-smooth muscle actin (alpha-SMA), transforming growth factor-beta (TGF-beta), and kidney injury molecule-1 (KIM-1) expression in the renal cortex. In summary, we have developed a tacrolimus-induced kidney injury rat model with interstitial fibrosis within 2 weeks by creating conditions mimicking renal transplantation via tacrolimus administration following ischemia-reperfusion. (C) 2021 Elsevier B.V. All rights reserved.