Effects of thrombopoietin pre-treatment on peri-liver transplantation thrombocytopenia in a mouse model of cirrhosis with hypersplenism  

作　　者：Zi-Rong Liu Ya-Min Zhang Zi-Lin Cui Wen Tong 

机构地区：[1]Department of Hepatobiliary Surgery,Tianjin First Central Hospital,Tianjin 300070,China

出　　处：《World Journal of Gastrointestinal Surgery》2023年第10期2115-2122,共8页世界胃肠外科杂志（英文版）（电子版）

基　　金：All procedures involving animals were reviewed and approved by the Tianjin Tiancheng New Drug Evaluation Co.,Ltd(Approval No.2023041701).

摘　　要：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 pat

关 键 词：Thrombopoietin pre-treatment CIRRHOSIS Liver transplantation Perioperative period PLATELET 

分 类 号：R575[医药卫生—消化系统] R558.2[医药卫生—内科学]