Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 21, 2019; 25(11): 1355-1365
Published online Mar 21, 2019. doi: 10.3748/wjg.v25.i11.1355
Hemodynamic changes in hepatic sinusoids of hepatic steatosis mice
Jing Fan, Chong-Jiu Chen, Yu-Chen Wang, Wei Quan, Jian-Wei Wang, Wei-Guang Zhang
Jing Fan, Chong-Jiu Chen, Yu-Chen Wang, Wei Quan, Jian-Wei Wang, Wei-Guang Zhang, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
Author contributions: Fan J and Chen CJ performed the majority of experiments and analyzed the data; Wang YC and Quan W performed the hemorheological investigation; Fan J, Chen CJ, and Wang JW participated equally in treatment of animals; Fan J and Chen CJ designed and coordinated the research; Chen CJ wrote the paper.
Supported by Beijing Municipal Natural Science Foundation, No. 7162098.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Peking University (IACUC protocol number: SCXK 2016-0010).
Conflict-of-interest statement: There is no conflict of interest in this study.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This is an open-access article that 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:
Corresponding author: Wei-Guang Zhang, MD, PhD, Professor, Department of Anatomy and Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, No. 38, Xueyuan Road, Haidian District, Beijing 100191, China.
Telephone: +86-10-82802969 Fax: +86-10-82802969
Received: December 19, 2018
Peer-review started: December 21, 2018
First decision: January 23, 2019
Revised: January 31, 2019
Accepted: February 22, 2019
Article in press: February 22, 2019
Published online: March 21, 2019
Research background

Despite the high incidence of fatty liver, there was no specific diagnosis and treatment. And the study of morphological and medical physics changes in fatty liver have been ignored for many years. It has been reported that hemodynamic changes occur in steatosis stage, which might be caused by the compression of the liver microcirculation and changes in the hemorheology characteristics.

Research motivation

Re-examining steatosis from a new perspective - hemodynamics - may enhance our understanding of fatty liver and provide a new idea of treatment.

Research objectives

We mainly focused on the microcirculation of the liver in steatosis stage, which cannot be detected by clinical imaging technique. By the two-photon fluorescence microscopy imaging technique, we observed the structure and hemodynamic characteristics of the liver sinusoids, which linked microscopic morphology with hemodynamics and complemented laboratory imaging to fill gaps in clinical imaging.

Research methods

A hepatic steatosis model was established by subcutaneous injection of carbon tetrachloride in mice. After establishing the model, liver tissue from mice was stained with hematoxylin and eosin (HE) and oil red O stains. Blood was collected from the angular vein, and hemorheological parameters were estimated. A two-photon fluorescence microscope was used to examine the flow properties of red blood cells in the hepatic sinusoids. All result values are presented on graphs as the mean ± SEM. The comparison between multiple groups was performed by one-way ANOVA followed by Dunnett's multiple comparison Test. P-values < 0.05 were considered statistically significant.

Research results

Oil red O staining indicated lipid accumulation in the liver after CCl4 treatment. HE staining indicated narrowing of the hepatic sinusoidal vessels. No significant difference was observed between the 2-wk and 4-wk groups of mice on morphological examination. Hemorheological tests revealed pathological changes in plasma components and red blood cells of hepatic steatosis. Assessment of blood flow velocity in the hepatic sinusoids revealed that as the modeling time increased, the blood flow velocity in the hepatic sinusoids decreased gradually; meanwhile, the diameter of the hepatic sinusoids became smaller.

These results revealed that hemodynamic changes occurring during steatosis stage (at least in the early stage) were more likely caused by sinusoidal deformation, but the mechanism of these phenomena remains to be solved.

Research conclusions

We used two-photon fluorescence microscopy imaging technique to study hemodynamic changes in fatty liver. And we observed that hemorheological change occurred in hepatic steatosis stage, and manifested as changes in blood flow velocity. We found that this change may be mainly caused by sinusoidal deformation, although it is related to hemorheology characteristics, but there was no statistical difference.

Research perspectives

Two-photon fluorescence microscopy imaging technique provides us with another way to observe microcirculation in addition to electron microscopy, and can be used to display stereoscopic blood vessel morphology through 3D reconstruction. In the future, it can be combined with magnetic resonance imaging and other fine imaging techniques to completely reconstruct the liver circulation through 3D printing, which will be a major breakthrough in the development of liver hemodynamics.