From the Robley Rex Louisville Veterans Affairs Medical Center (J.E.S., P.J.M., J.W.S.), and Department of Surgery (J.E.S., P.J.M., B.G.H., L.B., J.W.S.), Department of Physiology and Biophysics (J.E.S., P.J.M., J.W.M.), University of Louisville, Louisville, Kentucky; and Eastern Kentucky University (G.R.A.).
J Trauma Acute Care Surg. 2021 Jan 1;90(1):27-34. doi: 10.1097/TA.0000000000002916.
Hemorrhagic shock (HS) and resuscitation (RES) cause ischemia-induced intestinal permeability due to intestinal barrier breakdown, damage to the endothelium, and tight junction (TJ) complex disruption between enterocytes. The effect of hemostatic RES with blood products on this phenomenon is unknown. Previously, we showed that fresh frozen plasma (FFP) RES, with or without directed peritoneal resuscitation (DPR) improved blood flow and alleviated organ injury and enterocyte damage following HS/RES. We hypothesized that FFP might decrease TJ injury and attenuate ischemia-induced intestinal permeability following HS/RES.
Sprague-Dawley rats were randomly assigned to groups (n = 8): sham; crystalloid resuscitation (CR) (HS of 40% mean arterial pressure for 60 minutes) and CR (shed blood plus two volumes of CR); CR and DPR (intraperitoneal 2.5% peritoneal dialysis fluid); FFP (shed blood plus one volume of FFP); and FFP and DPR (intraperitoneal dialysis fluid plus two volumes of FFP). Fluorescein isothiocyanate-dextran (molecular weight, 4 kDa; FD4) was instilled into the gastrointestinal tract before hemorrhage; FD4 was measured by UV spectrometry at various time points. Plasma syndecan-1 and ileum tissue TJ proteins were measured using enzyme-linked immunosorbent assay. Immunofluorescence was used to visualize claudin-4 concentrations at 4 hours following HS/RES.
Following HS, FFP attenuated FD4 leak across the intestine at all time points compared with CR and DPR alone. This response was significantly improved with the adjunctive DPR at 3 and 4 hours post-RES (p < 0.05). Resuscitation with FFP-DPR increased intestinal tissue concentrations of TJ proteins and decreased plasma syndecan-1. Immunofluorescence demonstrated decreased mobilization of claudin-4 in both FFP and FFP-DPR groups.
Fresh frozen plasma-based RES improves intestinal TJ and endothelial integrity. The addition of DPR can further stabilize TJs and attenuate intestinal permeability. Combination therapy with DPR and FFP to mitigate intestinal barrier breakdown following shock could be a novel method of reducing ischemia-induced intestinal permeability and systemic inflammation after trauma.
Prognostic/Epidemiologic, Level III.
出血性休克（HS）和复苏（RES）会导致肠道屏障破裂、内皮损伤以及肠上皮细胞之间的紧密连接（TJ）复合物破坏，从而引起缺血性肠道通透性增加。使用血液制品进行止血性 RES 对这种现象的影响尚不清楚。此前，我们的研究表明，新鲜冷冻血浆（FFP）RES 可改善血流，并减轻 HS/RES 后的器官损伤和肠上皮细胞损伤，无论是联合还是不联合定向腹膜复苏（DPR）。我们假设 FFP 可能会减少 TJ 损伤并减轻 HS/RES 后的缺血性肠道通透性。
将 Sprague-Dawley 大鼠随机分为以下几组（n = 8）：假手术组；晶体液复苏（HS 为 40%平均动脉压 60 分钟）加晶体液复苏（失血加两倍体积的晶体液）；晶体液复苏加 DPR（腹腔内 2.5%腹膜透析液）；FFP 复苏（失血加 1 体积的 FFP）；FFP 复苏加 DPR（腹腔内透析液加两倍体积的 FFP）。在出血前将荧光素异硫氰酸酯-葡聚糖（分子量 4 kDa；FD4）注入胃肠道，通过紫外分光光度计在不同时间点测量 FD4。采用酶联免疫吸附试验测量血浆 syndecan-1 和回肠组织 TJ 蛋白。免疫荧光法在 HS/RES 后 4 小时观察 claudin-4 浓度。
与单独的 CR 和 DPR 相比，FFP 在 HS 后所有时间点均减轻了 FD4 漏过肠道的程度。在 RES 后 3 小时和 4 小时时，辅助 DPR 显著改善了这种反应（p < 0.05）。FFP-DPR 复苏增加了 TJ 蛋白在肠道组织中的浓度，并降低了血浆 syndecan-1。免疫荧光显示 claudin-4 在 FFP 和 FFP-DPR 两组中的动员均减少。
基于 FFP 的 RES 可改善肠道 TJ 和内皮完整性。DPR 的添加可以进一步稳定 TJ 并减轻肠道通透性。在休克后使用 DPR 和 FFP 联合治疗以减轻肠道屏障破坏，可能是减少创伤后缺血性肠道通透性和全身炎症的一种新方法。
预后/流行病学，III 级。
