Complement activation targeted inhibitor C2-FH ameliorates acetaminophen-induced liver injury in mice

补体激活靶向抑制剂 C2-FH 改善小鼠对乙酰氨基酚诱导的肝损伤

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作者:Chun-Mei Li, Tian Sun, Mou-Jie Yang, Zhi Yang, Qing Li, Jia-Lin Shi, Chong Zhang, Jun-Fei Jin

Aim

To explore C2-FH in protecting against APAP-induced liver injury by inhibiting complement activation.

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.

Conclusion

C2-FH attenuates 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.

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