坏死性下垂
医学
坏死
肺
移植
肿瘤坏死因子α
肺移植
再灌注损伤
肺水肿
缺血
水肿
内科学
药理学
免疫学
程序性细胞死亡
细胞凋亡
生物
生物化学
作者
Takashi Kanou,Akihiro Ohsumi,Hyunhee Kim,Manyin Chen,Xiaohui Bai,Z. Guan,David Hwang,Marcelo Cypel,Shaf Keshavjee,Mingyao Liu
标识
DOI:10.1016/j.healun.2018.04.005
摘要
Increasing evidence indicates that regulated necrosis plays a critical role during cell death caused by ischemia-reperfusion (IR) injury. Necroptosis is one form of regulated necrosis. Necrostatin-1 (Nec-1), an inhibitor of receptor-interacting protein kinase 1 (RIPK1), is known to reduce necroptosis. We investigated the effect of Nec-1 treatment on IR-induced lung injury in a rat lung transplant model.Lewis rats were divided into 4 groups (n = 6 each): (1) Control (no treatment), (2) Donor treatment (D), (3) Recipient treatment (R), and (4) Donor plus Recipient treatment (D+R) groups. Donor lungs were flushed and preserved for 18 hours at 4ºC before transplantation. Recipient animals underwent a left single lung transplant. After 2 hours of reperfusion, we assessed the physiologic function, cytokine expression, pathway activation, and the extent of necrosis.Pulmonary gas exchange in D+R group was significantly better than in the other 3 groups (p = 0.003). Lung edema was significantly lower in the D+R group compared with the Control group (p = 0.006). The expression of interleukin-6 in lung tissue and plasma was significantly reduced in the D+R group compared with the Control group (p = 0.036). The percentage of necrotic cells in D+R group was significantly lower than in the Control and D groups (p = 0.01), indicating Nec-1inhibited regulated necrosis.The administration of Nec-1 to both donor and recipient improved graft function after lung transplantation through the reduction of necroptosis. The inhibition of regulated necrosis appears to be a promising strategy to attenuate IR lung injury after lung transplantation.
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