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Murine model of long-term obstructive jaundice
Hiroaki Aoki1, Masayo Aoki1, Jing Yang2
1Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, Virginia; Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
The Journal of Surgical Research
|December 6, 2016
Summary
Developing a reliable murine model for long-term obstructive jaundice is crucial for cancer research. The ligation of left and median hepatic bile ducts with gallbladder removal (LMHL) offers sustained jaundice and feasibility for extended studies.
Area of Science:
- Hepatology
- Oncology
- Surgical Pathology
Background:
- Conjugated bile acids are emerging as critical signaling molecules in cancer development.
- There is a need for a murine model of obstructive jaundice that allows for long-term survival.
- Investigating different surgical ligation techniques is essential for establishing such a model.
Purpose of the Study:
- To characterize three distinct murine models of obstructive jaundice.
- To evaluate the feasibility of each model for long-term studies.
- To identify the most suitable model for investigating the effects of prolonged obstructive jaundice.
Main Methods:
- Three murine models were created: total common bile duct ligation (tCL), partial common bile duct ligation (pCL), and ligation of left/median hepatic bile ducts with gallbladder removal (LMHL).
- Survival rates were assessed using the Kaplan-Meier method.
- Fibrotic changes were evaluated via Masson-Trichrome staining and collagen expression analysis.
Main Results:
- The tCL model exhibited high mortality (70%) within 7 days.
- The pCL model showed rapid jaundice resolution in survivors, limiting its use for long-term studies.
- The LMHL model demonstrated prolonged jaundice beyond 14 days, with survival exceeding one month, and developed portal hypertension and severe fibrosis.
Conclusions:
- The standard tCL model is unsuitable for long-term obstructive jaundice research due to high mortality.
- The pCL model is appropriate for acute inflammation studies but not for sustained jaundice.
- The LMHL model is the most feasible for studying the long-term effects of obstructive jaundice and its role in cancer signaling.
