Cryoprecipitate attenuates the endotheliopathy of trauma in mice subjected to hemorrhagic shock and trauma.
Cryoprecipitate attenuates the endotheliopathy of trauma in mice subjected to hemorrhagic shock and trauma.
复制标题
冷冻沉淀减弱了受到出血性休克和创伤的小鼠创伤的内皮病。
DOI：
10.1097/ta.0000000000003164
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发表时间：
2021-06-01
期刊：
影响因子：
--
通讯作者：
Pati S
中科院分区：
文献类型：
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作者：
Barry M;Trivedi A;Miyazawa BY;Vivona LR;Khakoo M;Zhang H;Pathipati P;Bagri A;Gatmaitan MG;Kozar R;Stein D;Pati S
血浆已被证明可以减轻创伤的内皮病（EOT）。内皮的保护可能部分是由于纤维蛋白原和其他血浆衍生的蛋白质中发现的冷沉淀，但确切的机制仍然未知。临床试验正在调查早期冷沉淀管理创伤。在这项研究中，我们假设，冷沉淀将抑制内皮细胞（EC）的渗透性在体外，并复制血浆的能力，以减轻肺血管通透性和失血性休克和创伤（HS/T）诱导的炎症小鼠。在体外，内皮细胞的屏障通透性进行凝血酶的挑战，通过跨内皮电阻测量。在体内，使用已建立的HS/T小鼠模型，我们比较了用1）乳酸林格氏（LR），2）新鲜冷冻血浆（FFP）或3）冷沉淀复苏的小鼠之间的肺血管通透性。通过NanoString mRNA定量分析来自所有组中的小鼠的肺组织的血管完整性、炎症和炎症基因表达的标志物。冷沉淀以剂量依赖性方式减弱凝血酶诱导的EC通透性和EC连接受损。在体内，用FFP或冷沉淀物复苏HS/T小鼠减弱肺血管通透性（假手术：297±155，LR：848±331，FFP：379±275，冷沉淀物：405±207; p<0.01假手术vs. LR，p<0.01 LR vs. FFP，p<0.05 LR vs.冷沉淀物）。与LR处理的小鼠相比，来自冷沉淀和FFP处理的小鼠的肺表现出减少的肺损伤、减少的中性粒细胞浸润和巨噬细胞活化，以及保留的周细胞-内皮相互作用。来自冷沉淀和FFP处理的小鼠的肺组织的基因分析表明，与LR处理的小鼠相比，炎性基因表达降低，特别是IL-1β和NLRP 3。我们的数据表明，冷沉淀物减弱EOT在HS/T类似于FFP。对活性成分及其作用机制的进一步研究是必要的。
Plasma has been shown to mitigate the endotheliopathy of trauma (EOT). Protection of the endothelium may be due in part to fibrinogen and other plasma-derived proteins found in cryoprecipitate, however the exact mechanisms remain unknown. Clinical trials are underway investigating early cryoprecipitate administration in trauma. In this study, we hypothesize that cryoprecipitate will inhibit endothelial cell (EC) permeability in vitro and will replicate the ability of plasma to attenuate pulmonary vascular permeability and inflammation induced by hemorrhagic shock and trauma (HS/T) in mice. In vitro, barrier permeability of ECs subjected to thrombin challenge was measured by trans-endothelial electrical resistance. In vivo, using an established mouse model of HS/T, we compared pulmonary vascular permeability among mice resuscitated with 1) lactated Ringer’s (LR), 2) fresh frozen plasma (FFP), or 3) cryoprecipitate. Lung tissue from the mice in all groups was analyzed for markers of vascular integrity, inflammation, and inflammatory gene expression via NanoString mRNA quantification. Cryoprecipitate attenuates EC permeability and EC junctional compromise induced by thrombin in vitro in a dose-dependent fashion. In vivo, resuscitation of HS/T mice with either FFP or cryoprecipitate attenuates pulmonary vascular permeability (sham: 297±155, LR: 848±331, FFP: 379±275, cryoprecipitate: 405±207; p<0.01 sham vs. LR, p<0.01 LR vs. FFP, and p<0.05 LR vs. cryoprecipitate). Lungs from cryoprecipitate- and FFP-treated mice demonstrate decreased lung injury, decreased infiltration of neutrophils and activation of macrophages, and preserved pericyte-endothelial interaction compared to LR-treated mice. Gene analysis of lung tissue from cryoprecipitate- and FFP-treated mice demonstrates decreased inflammatory gene expression, in particular IL-1β and NLRP3, compared to LR-treated mice. Our data suggest that cryoprecipitate attenuates the EOT in HS/T similar to FFP. Further investigation is warranted on active components and their mechanisms of action.