Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 28, 2018; 24(44): 5005-5012
Published online Nov 28, 2018. doi: 10.3748/wjg.v24.i44.5005
Development of a novel rat model of heterogeneous hepatic injury by injection with colchicine via the splenic vein
Yan-Yan Zhang, Chao-Xu Zhang, Yu Li, Xuan Jiang, Yong-Fang Wang, Yang Sun, Jun Wang, Wan-Ying Ji, Yi Liu
Yan-Yan Zhang, Medical Imaging Center, The Affiliated Hospital of Liaoning Traditional Chinese Medical University, Shenyang 110032, Liaoning Province, China
Yan-Yan Zhang, Yong-Fang Wang, Yang Sun, Jun Wang, Wan-Ying Ji, Yi Liu, Department of Radiology, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Chao-Xu Zhang, Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Yu Li, Xuan Jiang, Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Author contributions: Liu Y designed the research; Zhang YY, Li Y, and Jiang X performed the research; Wang YF contributed new reagents or analytic tools; Sun Y, Wang J, and Ji WY analyzed the data; Zhang YY and Zhang CX wrote the paper.
Supported by the Chinese National Natural Science Foundation, No. 81471719.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the First Hospital of China Medical University (No. AF-SOP-07-7.1-01).
Institutional animal care and use committee statement: All experimental procedures were performed in accordance with the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health. This study was approved by the animal care committee of our university.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The ARRIVE Guidelines have been adopted.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author to: Yi Liu, PhD, Professor, Department of Radiology, The First Hospital of China Medical University, Heping District, No. 155, Nanjing Street, Shenyang 110001, Liaoning Province, China. liuyicmu@sina.cn
Telephone: +86-18740085050 Fax: +86-24-83282859
Received: September 11, 2018
Peer-review started: September 11, 2018
First decision: October 11, 2018
Revised: October 20, 2018
Accepted: November 2, 2018
Article in press: November 2, 2018
Published online: November 28, 2018
ARTICLE HIGHLIGHTS
Research background

Heterogeneous hepatic injury is often exhibited in patients who will undergo liver resection, especially those accompanied by hepatitis and cirrhosis. Assessment of uneven hepatic function is essential for preventing postoperative liver failure. Until now, there has been no simple, safe, and effective method to evaluate heterogeneous hepatic injury due to the absence of an ideal animal model.

Research motivation

The development of a practical, reproducible animal model of heterogeneous hepatic injury is the basis for future studies that will ultimately benefit human clinical practice. In the present study, a novel rat model was established by injection with colchicine via the splenic vein, aiming at developing a practical model of heterogeneous hepatic injury. The heterogeneous injury between the left and right hepatic lobes was assessed on liver sections according to the histological scoring criteria, which was then correlated with the results of magnetic resonance imaging (MRI) using the sequences reported for evaluating hepatic injury.

Research objectives

To develop a practical rat model of heterogeneous hepatic injury which can be used for the future studies into human clinical parameters, such as quantitative analysis of the regional liver function, by injection with colchicine via the splenic vein.

Research methods

Seventy male Sprague-Dawley rats were randomly divided into a control group and a colchicine group. Colchicine (0.25%) was injected via the splenic vein to develop a rat model of heterogeneous hepatic injury. An equal volume of normal saline was injected via the splenic vein in the control group. After the operation, rats of the colchicine group were selected randomly for MRI examinations. Rats of the control group underwent MRI examinations. T2-weighted images (T2WI) and diffusion weighted imaging (DWI) were used to evaluate the heterogeneous hepatic injury. The heterogeneous injury between the left and right hepatic lobes was assessed on liver sections according to the histological scoring criteria, which was then correlated with the results of MRI study.

Research results

Obvious pathological changes of hepatic parenchyma were observed over time in the colchicine group. Hepatic injury scores were significantly different between the left and right lobes at each time point. There was a significant difference in apparent diffusion coefficient (ADC) of DWI and liver-to-muscle ratio (LMR) of T2WI between the left and right lobes in the colchicine group at each time point, and similar result was also observed between the colchicine and control groups. Besides, there were significant correlations between hepatic injury scores and ADC values or LMR. Some problems, such as the stability of the uneven hepatic injury influenced by individual differences of animals, and longitudinal changes that can be evaluated using MRI parameters obtained over time, remain to be solved.

Research conclusions

In this study, it was found that injection with colchicine via the splenic vein can be used to successfully develop a rat model of heterogeneous hepatic injury. The results of this study support that DWI and T2WI can potentially evaluate heterogeneous injury among liver lobes.

Research perspectives

Using this model, future studies are needed to explore other new techniques for assessing the uneven distribution of hepatic function and predicting the reserved liver function.