Clinical Trials Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2023; 29(35): 5154-5165
Published online Sep 21, 2023. doi: 10.3748/wjg.v29.i35.5154
Heparanase inhibition leads to improvement in patients with acute gastrointestinal injuries induced by sepsis
Ting-Ting Chen, Jia-Jun Lv, Ling Chen, Min Li, Li-Ping Liu
Ting-Ting Chen, Jia-Jun Lv, The First Clinical Medical School of Lanzhou University, Lanzhou University, Lanzhou 730000, Gansu Province, China
Ling Chen, Min Li, Li-Ping Liu, Department of Emergency Critical Care Medicine, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
Author contributions: Chen TT collected the clinical data for data analysis and mapping and drafted the manuscript; Lv JJ collected the blood samples from the patients and performed the flow cytometry; Chen L collected blood from the patients and completed the enzyme-linked immunosorbent assays; Li M screened the research subjects and carried out clinical interventions; Liu LP participated in the experimental design, supervised the experimental process and reviewed the experimental results; and all the authors have read and approved the final manuscript.
Supported by the Science and Technology Department of Gansu Province, No. 20JR5RA35; Science and Technology Project of Gansu Province, No. 22JR10KA009; Talent Innovation and Entrepreneurship Project of Science and Technology Bureau of Chengguan District, Lanzhou, No. 2020RCCX0030; and Lanzhou Science and Technology Development Guiding Plan Project, No. 2019-ZD-37.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Clinical Research (drugs, devices) of The First Hospital of Lanzhou University.
Clinical trial registration statement: This study is registered at Chinese Clinical Trial Registry (https://www.chictr.org.cn/). The registration identification number is ChiCTR2300072241.
Informed consent statement: All study participants or their legal guardians agreed to be enrolled in the study and provided consent (written or oral).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: This study is registered at Chinese Clinical Trial Registry (https://www.chictr.org.cn/), and the data is shared on this platform.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Open-Access: This article 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 NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Li-Ping Liu, MD, PhD, Doctor, Department of Emergency Critical Care Medicine, The First Hospital of Lanzhou University, No. 1 West Road, Donggang, Chengguan District, Lanzhou 730000, Gansu Province, China. liulipingldyy@126.com
Received: July 5, 2023
Peer-review started: July 5, 2023
First decision: August 10, 2023
Revised: August 23, 2023
Accepted: September 5, 2023
Article in press: September 5, 2023
Published online: September 21, 2023
Abstract
BACKGROUND

Patients with sepsis are at high risk for acute gastrointestinal injury (AGI), but the diagnosis and treatment of AGI due to sepsis are unsatisfactory. Heparanase (HPA) plays an important role in septic AGI (S-AGI), but its specific mechanism is not completely understood, and few clinical reports are available.

AIM

To explore the effect and mechanism of HPA inhibition in S-AGI patients.

METHODS

In our prospective clinical trial, 48 patients with S-AGI were randomly assigned to a control group to receive conventional treatment, whereas 47 patients were randomly assigned to an intervention group to receive conventional treatment combined with low molecular weight heparin. AGI grade, sequential organ failure assessment score, acute physiology and chronic health evaluation II score, D-dimer, activated partial thromboplastin time (APTT), anti-Xa factor, interleukin-6, tumour necrosis factor-α, HPA, syndecan-1 (SDC-1), LC3B (autophagy marker), intestinal fatty acid binding protein, D-lactate, motilin, gastrin, CD4/CD8, length of intensive care unit (ICU) stay, length of hospital stay and 28-d survival on the 1st, 3rd and 7th d after treatment were compared. Correlations between HPA and AGI grading as well as LC3B were compared. Receiver operator characteristic (ROC) curves were generated to evaluate the diagnostic value of HPA, intestinal fatty acid binding protein and D-lactate in S-AGI.

RESULTS

Serum HPA and SCD-1 levels were significantly reduced in the intervention group compared with the control group (P < 0.05). In addition, intestinal fatty acid-binding protein, D-lactate, AGI grade, motilin, and gastrin levels and sequential organ failure assessment score were significantly decreased (P < 0.05) in the intervention group. However, LC3B, APTT, anti-Xa factor, and CD4/CD8 were significantly increased (P < 0.05) in the intervention group. No significant differences in interleukin-6, tumour necrosis factor-α, d-dimer, acute physiology and chronic health evaluation II score, length of ICU stay, length of hospital stay, or 28-d survival were noted between the two groups (P > 0.05). Correlation analysis revealed a significant negative correlation between HPA and LC3B and a significant positive correlation between HPA and AGI grade. ROC curve analysis showed that HPA had higher specificity and sensitivity in diagnosis of S-AGI.

CONCLUSION

HPA has great potential as a diagnostic marker for S-AGI. Inhibition of HPA activity reduces SDC-1 shedding and alleviates S-AGI symptoms. The inhibitory effect of HPA in gastrointestinal protection may be achieved by enhanced autophagy.

Keywords: Sepsis, Acute gastrointestinal injury, Heparanase, Autophagy

Core Tip: Heparanase (HPA) plays an important role in the occurrence and development of septic acute gastrointestinal injury (S-AGI). Our experimental results show that HPA has great potential as a diagnostic marker for S-AGI. Inhibition of HPA activity reduces syndecan-1 shedding, reduces inflammatory response, improves coagulation and immune function, and alleviates S-AGI symptoms. The inhibitory effect of HPA on gastrointestinal protection may be achieved by increasing the level of autophagy.