实用肝脏病杂志 ›› 2017, Vol. 20 ›› Issue (3): 294-297.doi: 10.3969/j.issn.1672-5069.2017.03.010

• 肝衰竭 • 上一篇    下一篇

Orionin对急性肝衰竭小鼠的保护作用及其对肝组织细胞因子水平的影响*

邓怡林, 于合国, 施敏, 石翠翠, 范建高, 李光明   

  1. 200092 上海市 上海交通大学医学院附属新华医院消化内科(邓怡林,石翠翠,范建高,李光明); 同仁医院消化内科(施敏); 上海市计划生育科学研究所(于合国,刁华)
  • 收稿日期:2016-10-14 出版日期:2017-06-10 发布日期:2018-03-10
  • 通讯作者: 李光明,E-mail: ligm68@126.com
  • 作者简介:邓怡林,女,25,硕士研究生。主要从事肝损伤及肝纤维化的防治研究。E-mail: yilindeng1991@163.com
  • 基金资助:
    *国家自然科学基金资助项目(编号:81400631/81570549)

Effect of oridonin on hepatic cytokine levels in mice with LPS/D-Gal-induced acute liver failure

Deng Yilin, Yu Heguo, Shi Min, et al.   

  1. Department of Gastroenterology,Xinhua Hospital Affiliated to Jiaotong University School of Medicine,Shanghai 200092,China
  • Received:2016-10-14 Online:2017-06-10 Published:2018-03-10

摘要: 目的 探讨冬凌草甲素(Oridonin)对脂多糖/D-氨基半乳糖氨(LPS/D-Gal)联合诱导的急性肝衰竭(ALF)小鼠的保护作用及其对肝组织细胞因子水平的影响。方法 取150只小鼠,随机分成5组,每组 30 只。采用LPS/D-Gal腹腔注射建立小鼠ALF模型,设生理盐水对照组、Oridonin对照组、LPS/D-Gal诱导模型组和LPS/D-Gal处理及不同剂量Oridonin干预组。采用Real-time PCR法检测肝组织肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1α、IL-1β和IL-6 mRNA水平。结果 模型组小鼠48 h存活率为0.0% (0/30),而两个Oridonin干预组小鼠48 h存活率分别提高至64.5% (19/30)和80.6% (24/30,P<0.01); 组织病理学检查显示模型组小鼠肝细胞呈大块或/和亚大块坏死,肝小叶结构消失,残存肝细胞肿胀、空泡变性,肝窦肿胀充血,炎细胞浸润。Oridonin干预组小鼠肝细胞坏死、空泡变性和炎细胞浸润等较模型组有明显的改善;模型组小鼠血清ALT和AST水平分别为(345.3 ± 54.1) U/L和(500.2±53.5) U/L,明显高于对照组的[(42.3±0.6)U/L和(117.1±9.8)U/L,P<0.01],两个Oridonin干预组分别为 (303.9±39.5) U/L和(340.6±2.8) U/L及[(130.2±38.3) U/L和 (209.8±36.2) U/L,P<0.05];模型组小鼠肝组织TNF-α、IL-1α、IL-1β和IL-6 mRNA水平显著高于正常对照组(P<0.01),而两个Oridonin干预组肝组织TNF-α、IL-1α、IL-1β和IL-6 mRNA水平显著低于模型组 (P<0.01)。结论 Oridonin对LPS/D-Gal诱导的ALF小鼠具有显著的保护作用,其作用机制可能与降低肝组织细胞因子水平有关。

关键词: 急性肝衰竭, 脂多糖, D-氨基半乳糖氨, 冬凌草甲素, 细胞因子, 小鼠

Abstract: Objective To investigate the effect of oridonin on hepatic cytokine levels in mice with polysaccharide(LPS)/ D-galactosamine(D-Gal)-induced acute liver failure. Methods 150 mice were randomly divided into five groups(30 in each group),e.g.,normal,oridonin control,model,oridonin-intervened,and oridonin-intervened for 12 days. ALF model was established in C57BL/6 mice by intraperitoneal injection of LPS/D-Gal. Results The 48 h lethality rate in LPS/D-Gal-induced group reached an extremely high level of 100%. However,the 48 h survival rates in two oridonin-intervened groups were 64.5% (19/30) and 80.6% (24/30,P<0.01);The damage in liver tissues was ameliorated in mice pretreated with oridonin as compared with that in the model group;Serum ALT and AST levels in model group were(345.3±54.1) U/L and(500.2±53.5) u/L,significantly higher than those in control group[(42.3±0.6) U/L and(117.1±9.8) U/L,P<0.01] or in oridonin-treated group [(303.9±39.5) U/L and (340.6±2.8) U/L or [(130.2±38.3) U/L and (209.8±36.2) U/L,P<0.05];Administration of oridonin in mice with LPS/D-Gal-induced ALF significantly decreased mRNA levels of hepatic TNF-α,IL-1α, IL-1β and IL-6 compared with in model group(P<0.01). Conclusion Oridonin has a protective effect on mice with LPS/D-Gal-induced ALF,and the mechanism might be related to inhibition of hepatic cytokine activities.

Key words: Acute liver failure, Lipopolysaccharide, D-galactosamine, Oridonin, Cytokines, Mice