Wang Miaoshu, Zhong Danfeng, Dong Ping, Song Yukang
Department of Medical Intensive Care Unit, The First People's Hospital of Wenling, Taizhou, China.
J Cell Biochem. 2019 Feb;120(2):2007-2014. doi: 10.1002/jcb.27507. Epub 2018 Aug 30.
C-X-C chemokine receptor types 1/2 (CXCR1/2) is known to be activated in liver damage in acute-on-chronic liver failure; however, the role in lipopolysaccharide (LPS)-induced sepsis is unknown. The current study was designed to determine whether or not CXCR1/2 blockade with reparixin ameliorates acute lung injury (ALI) by affecting neuropeptides in a LPS-induced sepsis mouse model.
Male C57BL/6 mice (10 to 14-week old) were divided into sham, LPS, sham-R, and LPS-R groups. Bronchoalveolar lavage fluid (BALF) was collected and evaluated. The lung histopathology was assessed by immunocytochemistry staining. Western blot analysis was used to measure myeloperoxidase, substance P (SP), and vasoactive intestinal peptide.
LPS-induced animal models were ameliorated by cotreatment with a CXCR1/2 antagonist. Moreover, the protective effects of CXCR1/2 antagonists were attributed to the increased secretion of pro-opiomelanocortin and decreased the secretion of SP. Reparixin decreased the expression of necroptosis cell death markers induced by LPS.
The results of this study indicate that blockade of CXCR1/2 may represent a promising therapeutic strategy for the treatment of sepsis-associated ALI through regulation of neuropeptides and necroptosis.
已知C-X-C趋化因子受体1/2型（CXCR1/2）在慢加急性肝衰竭的肝损伤中被激活；然而，其在脂多糖（LPS）诱导的脓毒症中的作用尚不清楚。本研究旨在确定在LPS诱导的脓毒症小鼠模型中，用瑞帕霉素阻断CXCR1/2是否通过影响神经肽来改善急性肺损伤（ALI）。
将10至14周龄的雄性C57BL/6小鼠分为假手术组、LPS组、假手术-R组和LPS-R组。收集支气管肺泡灌洗液（BALF）并进行评估。通过免疫细胞化学染色评估肺组织病理学。采用蛋白质免疫印迹分析来测量髓过氧化物酶、P物质（SP）和血管活性肠肽。
用CXCR1/2拮抗剂联合治疗可改善LPS诱导的动物模型。此外，CXCR1/2拮抗剂的保护作用归因于促阿片黑素皮质素分泌增加和SP分泌减少。瑞帕霉素降低了LPS诱导的坏死性凋亡细胞死亡标志物的表达。
本研究结果表明，阻断CXCR1/2可能是一种有前景的治疗策略，可通过调节神经肽和坏死性凋亡来治疗脓毒症相关的ALI。
