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

Fatty liver (FL) is now a worldwide disease. For decades, researchers have been kept trying to elucidate the mechanism of FL at the molecular level, but rarely involve the study of morphology and medical physics. Traditionally, it was believed that hemodynamic changes occur only when fibrosis occurs, but it has been proved that these changes already show in steatosis stage, which may help to reveal the pathogenesis and its progress. Because the pseudolobules are not formed during the steatosis stage, this phenomenon may be caused by the compression of the liver microcirculation and changes in the hemodynamics.


To understand the pathogenesis of hepatic steatosis and to study the hemodynamic changes associated with hepatic steatosis.


Eight-week-old male C57BL/6 mice were divided into three groups randomly (control group, 2-wk group, and 4-wk group), with 16 mice per group. 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.


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 included whole blood viscosity (mPas, γ = 10 s-1/γ = 100 s-1) (8.83 ± 2.22/4.69 ± 1.16, 7.73 ± 2.46/4.22 ± 1.32, and 8.06 ± 2.88/4.22 ± 1.50), red blood cell volume (%) (51.00 ± 4.00, 42.00 ± 5.00, and 40.00 ± 3.00), the content of plasma fibrinase (g/L) (3.80 ± 0.50, 2.90 ± 0.80, and 2.30 ± 0.70), erythrocyte deformation index (%) (44.49 ± 5.81, 48.00 ± 15.29, and 44.36 ± 15.01), erythrocyte electrophoresis rate (mm/s per V/m) (0.55 ± 0.11, 0.50 ± 0.11, and 0.60 ± 0.20), revealing pathological changes in plasma components and red blood cells of hepatic steatosis. Assessment of blood flow velocity in the hepatic sinusoids with a laser Doppler flowmeter (mL/min per 100 g) (94.43 ± 14.64, 80.00 ± 12.12, and 67.26 ± 5.92) and two-photon laser scanning microscope (μm/s) (325.68 ± 112.66, 213.53 ± 65.33, and 173.26 ± 44.02) revealed that as the modeling time increased, the blood flow velocity in the hepatic sinusoids decreased gradually, and the diameter of the hepatic sinusoids became smaller (μm) (10.28 ± 1.40, 6.84 ± 0.93, and 5.82 ± 0.79).


The inner diameter of the hepatic sinusoids decreases along with the decrease in the blood flow velocity within the sinusoids and the changes in the systemic hemorheology.

Keywords: Hepatic steatosis, Hemodynamics, Hepatic sinusoids, Two-photon fluorescence microscopy, Carbon tetrachloride

Core tip: We evaluated the situation of blood flow in the hepatic sinusoids in hepatic steatosis mice, and found that both the velocity of the blood flow in the sinusoid and the diameter of the sinusoid decreased when the mice got fatty liver. Furthermore, we established the 3D imaging of the hepatic sinusoids to observe the sinusoids directly.