补体激活靶向抑制剂C2-FH改善对乙酰氨基酚诱导的小鼠肝损伤。
Complement activation targeted inhibitor C2-FH ameliorates acetaminophen-induced liver injury in mice.
作者信息
Li Chun-Mei, Sun Tian, Yang Mou-Jie, Yang Zhi, Li Qing, Shi Jia-Lin, Zhang Chong, Jin Jun-Fei
机构信息
Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, the Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China.
Guangxi Health Commission Key Laboratory of Basic Research in Sphingolipid Metabolism Related Diseases, the Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China.
出版信息
World J Hepatol. 2024 Oct 27;16(10):1188-1198. doi: 10.4254/wjh.v16.i10.1188.
BACKGROUND
Complement activation is recognized as an important factor in the progression of liver damage caused by acetaminophen (APAP). However, the role of the complement inhibitor C2-FH in APAP-induced liver injury remains unclear.
AIM
To explore C2-FH in protecting against APAP-induced liver injury by inhibiting complement activation.
METHODS
A model of APAP-induced liver injury was used to study the protective effect of C2-FH on liver injury. C2-FH was administered through intraperitoneal injection 30 minutes after APAP treatment. We detected the effects of C2-FH on liver function, inflammatory response and complement activation. Additionally, RNA-sequencing (RNA-Seq) analysis was conducted to understand the mechanism through which C2-FH provides protection against APAP-induced liver injury.
RESULTS
C2-FH inhibited the increase in serum alanine aminotransferase activity, aspartate aminotransferase activity and lactate dehydrogenase, and reduced liver tissue necrosis caused by APAP. Moreover, it attenuated the inflammatory response and inhibited complement activation in APAP-induced liver injury. RNA-Seq analysis provided additional explanations for the protective role of C2-FH against APAP-induced liver injury.
CONCLUSION
C2-FH attenuates APAP-induced liver injury by inhibiting complement activation.
背景
补体激活被认为是对乙酰氨基酚（APAP）所致肝损伤进展的一个重要因素。然而，补体抑制剂C2-FH在APAP诱导的肝损伤中的作用仍不清楚。
目的
通过抑制补体激活来探索C2-FH对APAP诱导的肝损伤的保护作用。
方法
采用APAP诱导的肝损伤模型来研究C2-FH对肝损伤的保护作用。在给予APAP治疗30分钟后通过腹腔注射给予C2-FH。我们检测了C2-FH对肝功能、炎症反应和补体激活的影响。此外，进行了RNA测序（RNA-Seq）分析以了解C2-FH对APAP诱导的肝损伤提供保护作用的机制。
结果
C2-FH抑制了血清丙氨酸氨基转移酶活性、天冬氨酸氨基转移酶活性和乳酸脱氢酶的升高，并减轻了APAP所致的肝组织坏死。此外，它减轻了炎症反应并抑制了APAP诱导的肝损伤中的补体激活。RNA-Seq分析为C2-FH对APAP诱导的肝损伤的保护作用提供了更多解释。
结论
C2-FH通过抑制补体激活减轻APAP诱导的肝损伤。
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