Blocking Complement Factor B Activation Reduces Renal Injury and Inflammation in a Rat Brain Death Model

阻断补体因子 B 激活可减少大鼠脑死亡模型中的肾脏损伤和炎症

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作者:Neeltina M Jager, Judith E van Zanden, Marta Subías, Henri G D Leuvenink, Mohamed R Daha, Santiago Rodríguez de Córdoba, Felix Poppelaars, Marc A Seelen

Conclusion

This study shows that donor pretreatment with anti-FB preserved renal function, reduced renal damage and inflammation prior to transplantation. Therefore, inhibition of factor B in organ donors might be a promising strategy to reduce brain death-induced renal injury and inflammation.

Results

Pretreatment with anti-FB resulted in significantly less systemic and local complement activation than in saline-treated rats after brain death. Moreover, anti-FB treatment preserved renal function, reflected by significantly reduced serum creatinine levels compared to saline-treated rats after 4 h of brain death. Furthermore, anti-FB significantly attenuated histological injury, as seen by reduced tubular injury scores, lower renal gene expression levels (>75%) and renal deposition of kidney injury marker-1. In addition, anti-FB treatment significantly prevented renal macrophage influx and reduced systemic IL-6 levels compared to saline-treated rats after brain death. Lastly, renal gene expression of IL-6, MCP-1, and VCAM-1 were significantly reduced in rats treated with anti-FB.

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