肝脏 ›› 2017, Vol. 22 ›› Issue (11): 1008-1012.

• 论著 • 上一篇    下一篇

促红素衍生肽对刀豆蛋白A诱导的小鼠急性肝损伤的保护作用

吴盛迪,杨橙,沈锡中   

  1. 200032 上海 复旦大学附属中山医院消化科
  • 出版日期:2017-11-15 发布日期:2020-06-15
  • 通讯作者: 吴盛迪,Email:wu.shengdi@zs-hospital.sh.cn
  • 基金资助:
    国家自然科学基金资助项目(81500457)

The protective effects of helix B surface peptide on concanavalin A-induced acute liver injury in mice model

WU Sheng-di, YANG Cheng, SHEN Xi-zhong   

  1. Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, China
  • Online:2017-11-15 Published:2020-06-15
  • Contact: WU Sheng-di, Email:wu.shengdi@zs-hospital.sh.cn

摘要: 目的 探讨外源性给予人工合成的促红素衍生肽(HBSP)对刀豆蛋白A(Con A)诱导的急性免疫性肝损伤的保护作用。方法 采用小鼠尾静脉注射Con A建立急性肝损伤模型,造模后2 h给予HBSP治疗(采用尾静脉注射,8 nmol/kg,每6小时1次),造模后6、12、24 h分别测定小鼠血清中ALT、AST水平,并进行肝组织病理学检查评估肝损伤程度。测定造模后12 h肝组织中IL-6、IL-1β、TNF-α、IFN-γ、IL-12、IL-4、IL-10、TGF-β表达水平,通过TUNEL及免疫组化检测(分裂型Caspase-3)评估肝脏内肝细胞凋亡情况。结果 在Con A诱导的急性肝损伤小鼠模型中,HBSP给药组血清ALT和AST水平显著低于Con A模型组,并且小鼠肝组织炎症坏死程度明显低于Con A模型组。同时,80 nmol/kg的HBSP给药显著提高了注射致死剂量Con A小鼠的生存率。此外,HBSP在mRNA水平抑制肝脏中促炎因子(IL-6、IL-1β、TNF-α、IFN-γ、IL-12)的表达,促进抑炎因子(IL-4、IL-10)的表达,并显著抑制Con A诱导的急性肝损伤相关的细胞凋亡。结论 HBSP对Con A诱导的急性肝损伤具有较好的保护作用,其机制可能与其抑制炎性反应及肝细胞凋亡有关。

关键词: 促红素衍生肽, 刀豆蛋白A, 急性肝损伤, 炎症, 凋亡

Abstract: Objective To investigate the protective effects of helix B surface peptide (HBSP) on concanavalin A (Con A)-induced acute liver injury (ALI) in mice.Methods ALI mice was induced with Con A administration. Two hours later, intravenous injection of HBSP was carried out every 6 h with the dose of 8 nmol·kg-1. Serum and liver tissue samples were collected at 6 h, 12 h, and 24 h after Con A administration for evaluating liver function and histopathology. Inflammatory cell infiltration and cytokines were examined at 12 h, and hepatocytes apoptosis was measured using TUNEL analysis and immunohistochemistry (cleaved caspase-3). .Results Compared with Con A administration without HBSP treatment mice, HBSP treatment group showed significantly decreased levels of alanine aminotransferase and aspartate aminotransferase in serum and pro-inflammatory cytokines in liver tissues, as well as less hepatocyte apoptosis. Furthermore, HBSP improved the survival among those mice with ALI induced by Con A. Immunohistochemical staining indicated that HBSP relieved hepatocyte necrosis with the significantly decreased expression of cleaved caspase-3 in liver tissues, which was confirmed in TUNEL analysis.Conclusion HBSP is a potential therapeutic agent against Con A induced ALI, which might be associated with the inhibition of liver inflammation and hepatocyte apoptosis.

Key words: Helix B surface peptide, Concanavalin A, Acute liver injury, Inflammation, Apoptosis.