Olaparib attenuates sepsis-induced acute multiple organ injury via ERK-mediated CD14 expression
Olaparib attenuates sepsis-induced acute multiple organ injury via ERK-mediated CD14 expression
复制标题
奥拉帕尼通过 ERK 介导的 CD14 表达减轻脓毒症引起的急性多器官损伤
DOI：
10.1177/15353702211015620
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发表时间：
2021-05-29
影响因子：
3.2
通讯作者：
Li, Quan
中科院分区：
文献类型：
--
作者：
Chen, Zhixia;Chen, Yihui;Li, Quan
败血症的特征是持续的全身性炎症，这会导致多器官功能障碍。聚聚合酶-1抑制剂Olaparib具有抗炎特性。这项研究旨在评估Olaparib（治疗前和后处理）对败血症的影响，并研究它是否可以通过多菌血性败血症和腹膜巨噬细胞模型中的ERK途径抑制CD14表达。败血症是通过C57BL/6雄小鼠的盲肠结扎和穿刺诱导的。将五十只小鼠随机分为五组：假手术组用媒介物或奥拉帕里（Olaparib）治疗，盲肠连接和穿刺组与媒介物或Olaparib（5 mg/kg i.p.）或手术后2小时1小时。 Olaparib预处理显着提高了化粪池小鼠的存活率（P <0.001）。用Olaparib对小鼠进行治疗前后，通过减少促炎性介质TNF-Alpha和IL-6的量以及血清中的细菌负担，部分缓解了Cecal结扎和穿刺诱导的器官损伤，腹膜腔液体和Organs（P <0.05）。 Olaparib的保护作用通过抑制ERK激活与CD14抑制有关。 Olaparib促进了ERK介导的CD14表达的负调节，这可能导致败血症中的多器官损伤。
Sepsis is characterized by persistent systemic inflammation, which can cause multi-organ dysfunction. The poly polymerase-1 inhibitor olaparib possesses anti-inflammatory properties. This study aimed to assess the effects of olaparib (pre- and post-treatments) on sepsis, and to investigate whether it could suppress CD14 expression via the ERK pathway in polymicrobial sepsis and peritoneal macrophages models. Sepsis was induced by cecal ligation and puncture in C57BL/6 male mice. Fifty mice were randomly divided into five groups: The sham group was treated with vehicle or olaparib, the cecal ligation and puncture group with vehicle or with olaparib (5 mg/kg i.p.) 1 h before or 2 h after surgery. Olaparib pretreatment significantly improved the survival of septic mice (P < 0.001). Pre- and post-treatment of mice with olaparib partly alleviated cecal ligation and puncture-induced organ injury by decreasing the amounts of the pro-inflammatory mediators TNF-alpha and IL-6 as well as bacterial burden in the serum, peritoneal lavage fluid, and organs (P < 0.05). The protective effect of olaparib was associated with CD14 suppression via inhibition of ERK activation. Olaparib facilitated negative regulation of ERK-mediated CD14 expression, which may contribute to multi-organ injury in sepsis.