A mouse model of renal fibrosis to overcome the technical variability in ischaemia/reperfusion injury among operators

Abstract The ischaemia-reperfusion (I/R) model is a widely used model of acute kidney injury (AKI) and renal fibrosis. However, the ischaemia duration that is long enough to cause broad fibrosis shows that a high mortality rate and a short ischaemia duration does not cause fibrosis, resulting in a l...

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Autores principales: Yu Guan, Daisuke Nakano, Yifan Zhang, Lei Li, Ye Tian, Akira Nishiyama
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Lenguaje:EN
Publicado: Nature Portfolio 2019
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Acceso en línea:https://doaj.org/article/06794ee2989743df94faeada2768443f
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spelling oai:doaj.org-article:06794ee2989743df94faeada2768443f2021-12-02T15:09:27ZA mouse model of renal fibrosis to overcome the technical variability in ischaemia/reperfusion injury among operators10.1038/s41598-019-46994-z2045-2322https://doaj.org/article/06794ee2989743df94faeada2768443f2019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-46994-zhttps://doaj.org/toc/2045-2322Abstract The ischaemia-reperfusion (I/R) model is a widely used model of acute kidney injury (AKI) and renal fibrosis. However, the ischaemia duration that is long enough to cause broad fibrosis shows that a high mortality rate and a short ischaemia duration does not cause fibrosis, resulting in a large variation in fibrosis progression in this experimental model. Inter-operator variation occurs for I/R injury severity because the I/R procedure is complex, which results in poor reproducibility of subsequent fibrosis in the model. In the present study, we developed a renal fibrosis model in which the fibrosis progression for 8 weeks is predictable within 8 days. Three operators independently performed I/R followed by uninephrectomy at day 7 in mice. The aim was to create a model that would show a blood urea nitrogen (BUN) level >100 mg/dL at day 8 after I/R (day 1 after uninephrectomy). Although the ischaemia duration to satisfy this BUN criterion differed among operators, the mice developed anaemia, polyuria, and fibrosis in a similar manner under the same BUN criterion with a low mortality rate. Interstitial fibrosis had developed at week 8, which was strongly correlated with the BUN at day 8. This protocol allows operators to adjust the ischaemia duration based on the BUN criterion and to separate mice into the desired number of groups based on the BUN to study interventions against renal fibrosis.Yu GuanDaisuke NakanoYifan ZhangLei LiYe TianAkira NishiyamaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-9 (2019)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yu Guan
Daisuke Nakano
Yifan Zhang
Lei Li
Ye Tian
Akira Nishiyama
A mouse model of renal fibrosis to overcome the technical variability in ischaemia/reperfusion injury among operators
description Abstract The ischaemia-reperfusion (I/R) model is a widely used model of acute kidney injury (AKI) and renal fibrosis. However, the ischaemia duration that is long enough to cause broad fibrosis shows that a high mortality rate and a short ischaemia duration does not cause fibrosis, resulting in a large variation in fibrosis progression in this experimental model. Inter-operator variation occurs for I/R injury severity because the I/R procedure is complex, which results in poor reproducibility of subsequent fibrosis in the model. In the present study, we developed a renal fibrosis model in which the fibrosis progression for 8 weeks is predictable within 8 days. Three operators independently performed I/R followed by uninephrectomy at day 7 in mice. The aim was to create a model that would show a blood urea nitrogen (BUN) level >100 mg/dL at day 8 after I/R (day 1 after uninephrectomy). Although the ischaemia duration to satisfy this BUN criterion differed among operators, the mice developed anaemia, polyuria, and fibrosis in a similar manner under the same BUN criterion with a low mortality rate. Interstitial fibrosis had developed at week 8, which was strongly correlated with the BUN at day 8. This protocol allows operators to adjust the ischaemia duration based on the BUN criterion and to separate mice into the desired number of groups based on the BUN to study interventions against renal fibrosis.
format article
author Yu Guan
Daisuke Nakano
Yifan Zhang
Lei Li
Ye Tian
Akira Nishiyama
author_facet Yu Guan
Daisuke Nakano
Yifan Zhang
Lei Li
Ye Tian
Akira Nishiyama
author_sort Yu Guan
title A mouse model of renal fibrosis to overcome the technical variability in ischaemia/reperfusion injury among operators
title_short A mouse model of renal fibrosis to overcome the technical variability in ischaemia/reperfusion injury among operators
title_full A mouse model of renal fibrosis to overcome the technical variability in ischaemia/reperfusion injury among operators
title_fullStr A mouse model of renal fibrosis to overcome the technical variability in ischaemia/reperfusion injury among operators
title_full_unstemmed A mouse model of renal fibrosis to overcome the technical variability in ischaemia/reperfusion injury among operators
title_sort mouse model of renal fibrosis to overcome the technical variability in ischaemia/reperfusion injury among operators
publisher Nature Portfolio
publishDate 2019
url https://doaj.org/article/06794ee2989743df94faeada2768443f
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