Bai Li, Jin Waishu, Kong Ming, Zhang Xiaohui, Zheng Sujun, Chen Yu, Li Lu, Liu Hui, Zhu Longdong, Ren Feng, Li Junfeng, Han Yuanping, Duan Zhongping
Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
Dig Dis. 2018;36(2):167-176. doi: 10.1159/000480426. Epub 2017 Sep 14.
Injury resistance occurring in the setting of liver fibrosis is an interesting phenomenon not yet well characterized. In the present study, we investigated dynamically the injury resistance against acute challenge using animal models of hepatic fibrosis and spontaneous resolution, and focused on high-mobility group box-1 (HMGB1), an important proinflammatory mediator.
The hepatic damage of control, fibrosis (CCl4, 6 weeks), and regressive mice with or without CCl4 challenge was dynamically observed and compared. The translocation and release of HMGB1 were assessed by immunohistochemical staining and enzyme-linked immunosorbent assay, respectively. The gene expression of proinflammatory mediators was detected by real-time PCR.
Our data showed that the fibrotic mice were invulnerable to acute CCl4 insult. The injury resistance diminished along with the resolution of liver fibrosis. Acute insult triggered the translocation and release of HMGB1 in control mice, which were remarkably inhibited in fibrotic mice, even under acute challenge. Nevertheless, regressive mice exhibited obvious translocation upon insult, especially for R12d mice. HMGB1-related proinflammatory immune responses were suppressed in fibrotic mice; however, they were restored in regressive mice upon insult.
The injury resistance in the setting of liver fibrosis is accompanied by the inhibition of HMGB1 translocation and release as well as the suppression of HMGB1-related proinflammatory immune responses.
肝纤维化背景下出现的损伤抵抗是一种尚未得到充分表征的有趣现象。在本研究中，我们使用肝纤维化和自然消退的动物模型动态研究了对急性挑战的损伤抵抗，并重点关注了重要的促炎介质高迁移率族蛋白B1（HMGB1）。
动态观察并比较了对照组、纤维化组（四氯化碳，6周）以及接受或未接受四氯化碳挑战的消退期小鼠的肝损伤情况。分别通过免疫组织化学染色和酶联免疫吸附测定评估HMGB1的转位和释放。通过实时PCR检测促炎介质的基因表达。
我们的数据表明，纤维化小鼠对急性四氯化碳损伤具有抗性。随着肝纤维化的消退，损伤抵抗能力减弱。急性损伤在对照组小鼠中引发了HMGB1的转位和释放，而在纤维化小鼠中，即使在急性挑战下，这种现象也受到显著抑制。然而，消退期小鼠在受到损伤时表现出明显的转位，尤其是R12d小鼠。纤维化小鼠中与HMGB1相关的促炎免疫反应受到抑制；然而，在消退期小鼠受到损伤后，这些反应得以恢复。
肝纤维化背景下的损伤抵抗伴随着HMGB1转位和释放的抑制以及与HMGB1相关的促炎免疫反应的抑制。
