15d-PGJ2 通过上调 HO-1 和减少肝细胞自噬来缓解 ConA 诱导的小鼠急性肝损伤。

15d-PGJ2 alleviates ConA-induced acute liver injury in mice by up-regulating HO-1 and reducing hepatic cell autophagy.

机构信息

Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.

Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; The First Clinical Medical College of Nanjing Medical University, Nanjing 210029, China.

出版信息

Biomed Pharmacother. 2016 May;80:183-192. doi: 10.1016/j.biopha.2016.03.012. Epub 2016 Mar 26.

DOI:10.1016/j.biopha.2016.03.012

PMID:27133055

Abstract

OBJECTIVE

In this study, we confirmed a protective effect of 15d-PGJ2 in concanavalin A (ConA)-induced fulminant hepatitis in mice and investigated the potential mechanism.

MATERIALS AND METHODS

Balb/C mice were injected with ConA (25mg/kg) to induce acute fulminant hepatitis, and 15d-PGJ2 (2.5-10μg) was administered 30min after the ConA injection. The histological grade, pro-inflammatory cytokine and ROS levels, apoptosis and autophagy activity, the expression of HO-1, Nrf2, JNK and Bcl-2 activity were determined 2, 4, and 8h after the ConA injection.

RESULTS

Following ConA challenge, the expression of cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) was up-regulated. Treatment with 15d-PGJ2 reduced the pathological effects of ConA-induced fulminant hepatitis and significantly reduced the levels of TNF-α, IL-1β and ROS after injection. 15d-PGJ2 inhibited apoptosis and autophagic cell death, facilitated Nrf2 nuclear translocation, increased HO-1 expression and suppressed the JNK activation.

CONCLUSION

15d-PGJ2 alleviates ConA-induced acute liver injury in mice by up-regulating the anti-oxidative stress factor HO-1 and reducing the production of cytokines and ROS, thereby inhibiting hepatic cell autophagy probably induced by ROS.

摘要

目的

本研究旨在确认 15d-PGJ2 在伴刀豆球蛋白 A（ConA）诱导的小鼠暴发性肝炎中的保护作用，并探讨其潜在机制。

材料与方法

Balb/C 小鼠注射 ConA（25mg/kg）诱导急性暴发性肝炎，在 ConA 注射后 30min 给予 15d-PGJ2（2.5-10μg）。在 ConA 注射后 2、4 和 8h 测定组织学分级、促炎细胞因子和 ROS 水平、凋亡和自噬活性、HO-1、Nrf2、JNK 和 Bcl-2 活性的表达。

结果

ConA 攻击后，细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素 1β（IL-1β）的表达上调。15d-PGJ2 治疗减轻了 ConA 诱导的暴发性肝炎的病理作用，并且在注射后显著降低了 TNF-α、IL-1β 和 ROS 的水平。15d-PGJ2 抑制凋亡和自噬性细胞死亡，促进 Nrf2 核易位，增加 HO-1 表达，并抑制 JNK 激活。