Partial Bile Duct Ligation in the Mouse: A Controlled Model of Localized Obstructive Cholestasis

Yokota, Shinichiro; Nakao, Toshimasa; Zhang, Peng; Michalopoulos, George K.; Khan, Zahida

doi:10.3791/56930

Cited by 18 publications

(23 citation statements)

References 23 publications

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“…88 In the last decade, modifications were also described of total BDL, including partial BDL and selective BDL. 85,87,89 Selective BDL is defined as ligating the left hepatic bile duct before it enters the common bile duct, while in partial BDL, a single ligation around the common bile duct is performed with leaving a defined lumen that allows a limited degree of bile flow. 87 The advantage of selective BDL is that the cholestatic injury is solely located in the left hepatic lobe, wherein bile infarcts develops as well as infiltrating neutrophils.…”

Section: Obstructive Cholestasismentioning

confidence: 99%

Rodent models of cholestatic liver disease: A practical guide for translational research

Gijbels

Pieters

Muynck

et al. 2021

Liver International

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Cholestatic liver disease denotes any situation associated with impaired bile flow concomitant with a noxious bile acid accumulation in the liver and/or systemic circulation. Cholestatic liver disease can be subdivided into different types according to its clinical phenotype, such as biliary atresia, drug‐induced cholestasis, gallstone liver disease, intrahepatic cholestasis of pregnancy, primary biliary cholangitis and primary sclerosing cholangitis. Considerable effort has been devoted to elucidating underlying mechanisms of cholestatic liver injuries and explore novel therapeutic and diagnostic strategies using animal models. Animal models employed according to their appropriate applicability domain herein play a crucial role. This review provides an overview of currently available in vivo animal models, fit‐for‐purpose in modelling different types of cholestatic liver diseases. Moreover, a practical guide and workflow is provided which can be used for translational research purposes, including all advantages and disadvantages of currently available in vivo animal models.

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Section: Obstructive Cholestasismentioning

confidence: 99%

Rodent models of cholestatic liver disease: A practical guide for translational research

Gijbels

Pieters

Muynck

et al. 2021

Liver International

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“…Mice were randomly allocated into the sham group ( n = 10) and model group ( n = 45). The mouse model of hepatic and renal fibrosis was established by BDL and UUO surgical operation under sterile conditions according to previous research ( Chevalier et al, 2009 ; Yokota et al, 2018 ). Briefly, experimental mice were anesthetized with isoflurane.…”

Section: Methodsmentioning

confidence: 99%

Total C-21 Steroidal Glycosides From Baishouwu Ameliorate Hepatic and Renal Fibrosis by Regulating IL-1β/MyD88 Inflammation Signaling

et al. 2021

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Fibrosis is a worldwide public health problem, which typically results from chronic diseases and often leads to organ malfunction. Chronic inflammation has been suggested to be the major trigger for fibrogenesis, yet mechanisms by which inflammatory signals drive fibrogenesis have not been fully elucidated. Total C-21 steroidal glycosides (TCSG) from Baishouwu are the main active components of the root of Cynanchum auriculatum Royle ex Wight, which exert hepatoprotective and anti-inflammation properties. In this study, we established a mouse model with the coexistence of hepatic and renal fibrosis and aimed to investigate the effects of TCSG from Baishouwu on fibrosis and explored the potential mechanisms. The results of biochemical and pathological examinations showed that TCSG from Baishouwu improved liver and kidney function and alleviated hepatic and renal fibrosis by reducing collagen and extracellular matrix deposition in bile duct ligation and unilateral ureteral occlusion (BDL&UUO) mice. According to network pharmacology analysis, the mechanisms underlying the effects of TCSG from Baishouwu on hepatic and renal fibrosis were associated with inflammatory response pathways, including “Signaling by interleukins”, “MAP kinase activation”, “MyD88 cascade initiated on plasma membrane”, and “Interleukin-1 family signaling”. Regression analysis and western blot results revealed that IL-1β/MyD88 inflammation signaling played an essential role in the anti-fibrotic effects of TCSG from Baishouwu. Further data displayed that TCSG from Baishouwu affected inflammatory response and extracellular matrix deposition via suppressing the activation of p38 MAPK/JNK and NF-κB p65 signaling cascades both in the liver and kidney of BDL&UUO mice. Thus, our findings suggest TCSG from Baishouwu as a natural regimen against hepatic and renal fibrosis and provide direct evidence that IL-1β/MyD88 signaling crucially contributes to hepatic and renal fibrosis and modulates liver-kidney crosstalk by maintaining tight control over inflammatory responses.

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“…Livers from sham‐operated and bile duct–ligated mice were collected at 3 days following ligation. In limited studies, partial bile duct ligation was done by looping a ligature around the common bile duct and an adjacent 7.0 surgical needle . When the ligature is tied carefully and the needle is removed, a reproducibly narrowed but defined lumen remained that results in cholestasis.…”

Section: Methodsmentioning

confidence: 99%

“…In limited studies, partial bile duct ligation was done by looping a ligature around the common bile duct and an adjacent 7.0 surgical needle. (13,14) When the ligature is tied carefully and the needle is removed, a reproducibly narrowed but defined lumen remained that results in cholestasis. All animals received humane care according to the criteria outlined in the Guide for the Care and Use of Laboratory Animals prepared by the National Academy of Sciences and published by the National Institutes of Health.…”

Section: Materials and Methods Animalsmentioning

confidence: 99%

Up‐regulation of miR‐let7a‐5p Leads to Decreased Expression of ABCC2 in Obstructive Cholestasis

et al. 2019

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Adenosine triphosphate–binding cassette subfamily C member 2 (ABCC2/Abcc2) is critically important to biliary excretion of many endobiotic and xenobiotic compounds, and is a major driving force for bile acid–independent bile flow. Abcc2 expression is reduced at the messenger RNA (mRNA) and protein levels in various forms of experimental cholestasis. In a microRNA (miRNA) screen of mouse liver after biliary obstruction, we found that miRNA let7a‐5p was significantly up‐regulated approximately 4‐fold. Similarly, ABCC2 mRNA was depleted and miRNA let7a‐5p was elevated over 4‐fold in livers of children with biliary atresia compared with normal livers. In silico analysis predicted that let7a‐5p would target the 3′ untranslated region (3′ UTR) of ABCC2/Abcc2 RNA. The objective of this study was to determine whether let7a‐5p contributes to the depletion of ABCC2/Abcc2 in cholestasis. To demonstrate the functional importance of miRNA let7a‐5p in regulating the expression of ABCC2, co‐transfection of a let7a‐5p mimic and an ABCC2‐3′ UTR luciferase construct into Huh‐7 cells led to a marked inhibition of luciferase activity by about 60%‐70% compared with controls, which was reversed by a let7a‐5p mimic inhibitor. Expression of this mimic led to a significant decrease in endogenous ABCC2 mRNA and protein levels in a Huh‐7 liver cell line, which could be blocked by expression of a let7a‐5p mimic inhibitor. Injection of a lentivirus let7a‐5p inhibitor into normal mouse liver or into mouse liver after common bile duct ligation led to a significant increase in endogenous Abcc2 mRNA and protein levels and a depletion of let7a‐5p mRNA levels compared with untreated, saline‐injected livers or livers treated with an inactive lentivirus control. Conclusion: These studies demonstrate that miR‐let7a‐5p is involved in regulating ABCC2/Abcc2 expression, and is aberrantly up‐regulated in obstructive cholestasis.

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Partial Bile Duct Ligation in the Mouse: A Controlled Model of Localized Obstructive Cholestasis

Cited by 18 publications

References 23 publications

Rodent models of cholestatic liver disease: A practical guide for translational research

Rodent models of cholestatic liver disease: A practical guide for translational research

Total C-21 Steroidal Glycosides From Baishouwu Ameliorate Hepatic and Renal Fibrosis by Regulating IL-1β/MyD88 Inflammation Signaling

Up‐regulation of miR‐let7a‐5p Leads to Decreased Expression of ABCC2 in Obstructive Cholestasis

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