肝脏 ›› 2025, Vol. 30 ›› Issue (6): 868-871.

• 其他肝病 • 上一篇    下一篇

TLR4单抗联合干细胞治疗改善热射病小鼠肝损伤

李平, 姚传霞, 邢继成, 杨志慧, 曹晓卉, 王君宜   

  1. 210002 南京 东部战区总医院秦淮医疗区肝病科(李平,姚传霞),检验科(邢继成),病理科(杨志慧,曹晓卉),干部病区(王君宜)
  • 收稿日期:2024-03-05 出版日期:2025-06-30 发布日期:2025-08-08
  • 通讯作者: 王君宜,Email:18900671312@139.com
  • 基金资助:
    东部战区总院院内课题(YYMS2021039&22JCYYYB7)

TLR4 monoclonal antibody combined with stem cell therapy improves liver injury in heat stroke mice

LI Ping1, YAO Chuan-xia1, XING Ji-cheng2, YANG Zhi-hui3, CAO Xiao-hui3, WANG Jun-yi4   

  1. 1. Department of Liver Disease, Qinhuai Medical District, General Hospital of the Eastern Theater, Nanjing 210002, China;
    2. Department of Clinical Laboratory, Qinhuai Medical District, General Hospital of the Eastern Theater, Nanjing 210002, China;
    3. Department of Pathology, Qinhuai Medical District, General Hospital of the Eastern Theater, Nanjing 210002, China;
    4. Cadre Ward, General Hospital of the Eastern Theater, Nanjing 210002, China
  • Received:2024-03-05 Online:2025-06-30 Published:2025-08-08
  • Contact: WANG Jun-yi, Email:18900671312@139.com

摘要: 目的 探讨在间充质干细胞基础上联合Toll样受体4(Toll-like receptor 4,TLR4)单抗治疗对热射病小鼠肝损伤的保护作用。方法 从活体小鼠腹股沟脂肪分离获取间充质干细胞,小鼠随机分为4组:空白对照组(control)、热射病组(HS)、干细胞干预组(MSC)、干细胞+TLR4单抗干预组(MT)。实验小鼠热射病造模成功后,HS组腹腔注射1 mL 0.9% 氯化钠注射液;MSC组注射2×106个MSCs。MT组注射2×106个MSC和100 μg TLR4单抗,小鼠再饲养7 d后,收集眼眶静脉血1 mL,生化仪进行血清ALT、AST检测,Elisa法检测炎症因子IL-1β、IL-6、TNF-α;同时处死小鼠取肝组织,固定后切片、HE染色。实验数据采用SPSS 19.0进行分析。结果 HS组小鼠肝组织病理显示肝细胞索排列紊乱,肝细胞中-重度浑浊伴空泡变性,部分肝细胞坏死,少量散在淋巴细胞浸润。MSC组小鼠肝组织可见肝细胞轻-中度肿胀,细胞间可见中等量空泡样结构。MT组小鼠肝组织损伤轻微。HS组小鼠的ALT和AST明显升高,分别为(347.3±130.5) U/L和(345.0±229.3) U/L,与其余各组相比差异有显著统计学意义(P<0.01);血清炎症因子IL-1β、IL-6、TNF-α水平分别为(185.44±143.64) pg/mL、(51.42±34.41) pg/mL和(83.94±54.24) pg/mL,与其他三组相比存在明显统计学差异,P值分别为0.003、0.011和0.016。结论 干细胞联合TLR4单抗治疗可通过NF-κB炎症信号通路改善热射病小鼠肝损伤;且联合治疗存在协同作用。

关键词: 热射病, 间充质干细胞, 单克隆抗体, 肝损伤

Abstract: Objective To investigate the protective effect of mesenchymal stem cells combined with TLR4 monoclonal antibody as the treatment of liver injury in heatstroke mice. Methods Mesenchymal stem cells were obtained from inguinal fat tissue separated from living mice. Mice were randomly divided into four groups: blank control group (control), heat stroke group (HS), stem cell intervention group (MSC), and stem cell+TLR4 antibody intervention group (MT). After the successful modeling of heat stroke in the experimental mice, 1 mL of 0.9% sodium chloride injection was injected intraperitoneally in the HS group. The MSC group was injected with 2×106 MSCs. In the MT group, 2×106 MSCs and 100 μg TLR4 monoclonal antibody were injected. After 7 days of refeeding, 1ml of orbital venous blood was collected, serum ALT and AST were detected by biochemical instrument, and inflammatory factors IL-1β, IL-6 and TNF-α were detected by Elisa method. At the same time, the mice were sacrificed to collect liver tissue, and the sections were fixed and stained with HE. SPSS 19.0 was used for the analysis of experimental data. Results The liver histopathology of HS group mice showed that the hepatocyte cord arrangement was disordered, the hepatocytes were moderately to severely turbid with vacuolar degeneration, some hepatocytes were necrosis, and a small amount of scattered lymphocyte infiltration. Mild to moderate turbidity of hepatocytes and moderate vacuolar structures were observed in the liver tissues of mice in the MSC group. The liver tissue damage of mice in the MT group was mild. The ALT and AST levels in the HS group mice were significantly increased, reaching 347.3 ± 130.5 U/L and 345.0 ± 229.3 U/L, respectively, with significant statistical differences compared to the other groups (P<0.01); Serum inflammatory cytokine IL-1 β, IL-6, TNF- α The levels were 185.44 ± 143.64 pg/mL, 51.42 ± 34.41 pg/mL, and 83.94 ± 54.24 pg/mL, respectively. There was a significant statistical difference compared to the other three groups, with P values of 0.003, 0.011, and 0.016, respectively. Conclusion Stem cell combined with TLR4 monoclonal antibody therapy improves liver injury in heat stroke mice through NF- κ B inflammatory signaling pathway; And the combination therapy has a synergistic effect.

Key words: Heat stroke disease, Mesenchymal stem cell, Monoclonal antibodies, Liver injury