Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Oct 27, 2023; 15(10): 2115-2122
Published online Oct 27, 2023. doi: 10.4240/wjgs.v15.i10.2115
Effects of thrombopoietin pre-treatment on peri-liver transplantation thrombocytopenia in a mouse model of cirrhosis with hypersplenism
Zi-Rong Liu, Ya-Min Zhang, Zi-Lin Cui, Wen Tong
Zi-Rong Liu, Ya-Min Zhang, Zi-Lin Cui, Wen Tong, Department of Hepatobiliary Surgery, Tianjin First Central Hospital, Tianjin 300070, China
Author contributions: Liu ZR, Cui ZL, and Tong W designed the research study; Liu ZR and Cui ZL performed the research; Liu ZR and Tong W contributed new reagents and analytic tools; Liu ZR and Cui ZL analyzed the data and wrote the manuscript; Zhang YM is responsible for reviewing the entire study; and all authors have read and approve the final manuscript.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Tianjin Tiancheng New Drug Evaluation Co., Ltd (Approval No. 2023041701).
Conflict-of-interest statement: All authors declare that there are no conflicts of interest.
Data sharing statement: The data of this study can be shared.
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 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: Ya-Min Zhang, MD, Doctor, Department of Hepatobiliary Surgery, Tianjin First Central Hospital, Fukang Road, Nankai District, Tianjin 300070, China. 5020200824@nankai.edu.cn
Received: July 6, 2023
Peer-review started: July 6, 2023
First decision: July 27, 2023
Revised: August 5, 2023
Accepted: August 25, 2023
Article in press: August 25, 2023
Published online: October 27, 2023
Processing time: 113 Days and 1 Hours
Abstract
BACKGROUND

During cirrhosis, the liver is impaired and unable to synthesize and clear thrombopoietin properly. At the same time, the spleen assumes the function of hemofiltration and storage due to liver dysfunction, resulting in hypersplenism and excessive removal of platelets in the spleen, further reducing platelet count. When liver function is decompensated in cirrhotic patients, the decrease of thrombopoietin (TPO) synthesis is the main reason for the decrease of new platelet production. This change of TPO leads to thrombocytopenia and bleeding tendency in cirrhotic patients with hypersplenism.

AIM

To investigate the clinical efficacy of recombinant human TPO (rhTPO) in the treatment of perioperative thrombocytopenia during liver transplantation in cirrhotic mice with hypersplenism.

METHODS

C57BL/6J mice and TPO receptor-deficient mice were used to establish models of cirrhosis with hypersplenism. Subsequently, these mice underwent orthotopic liver transplantation (OLT). The mice in the experimental group were given rhTPO treatment for 3 consecutive days before surgery and 5 consecutive days after surgery, while the mice in the control group received the same dose of saline at the same frequency. Differences in liver function and platelet counts were determined between the experimental and control groups. Enzyme-linked immunosorbent assay was used to assess the expression of TPO and TPO receptor (c-Mpl) in the blood.

RESULTS

Preoperative administration of rhTPO significantly improved peri-OLT thrombocytopenia in mice with cirrhosis and hypersplenism. Blocking the expression of TPO receptors exacerbated peri-OLT thrombocytopenia. The concentration of TPO decreased while the concentration of c-Mpl increased in compensation in the mouse model of cirrhosis with hypersplenism. TPO pre-treatment significantly increased the postoperative TPO concentration in mice, which in turn led to a decrease in the c-Mpl concentration. TPO pre-treatment also significantly enhanced the Janus kinase (Jak)/signal transducers and activators of transcription pathway protein expressions in bone marrow stem cells of the C57BL/6J mice. Moreover, the administration of TPO, both before and after surgery, regulated the levels of biochemical indicators, such as alanine aminotransferase, alkaline phosphatase, and aspartate aminotransferase in the C57BL/6J mice.

CONCLUSION

Pre-treatment with TPO not only exhibited therapeutic effects on perioperative thrombocytopenia in the mice with cirrhosis and hypersplenism, who underwent liver transplantation but also significantly enhanced the perioperative liver function.

Keywords: Thrombopoietin pre-treatment, Cirrhosis, Liver transplantation, Perioperative period, Platelet

Core Tip: Our research results confirm that thrombopoietin (TPO) can improve liver function after liver transplantation in mice by enhancing the effect of platelets. Pre-treatment with TPO not only exhibited therapeutic effects on perioperative thrombocytopenia in the mice with cirrhosis and hypersplenism, who underwent liver transplantation but also significantly enhanced the perioperative liver function.