Dual blockade of P-selectin and β2-integrin in the liver inflammatory response after uncontrolled hemorrhagic shock
Dual blockade of P-selectin and β2-integrin in the liver inflammatory response after uncontrolled hemorrhagic shock
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DOI：
10.1016/s1072-7515(98)00125-2
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发表时间：
1998-07-01
影响因子：
5.2
通讯作者：
Ward, PA
中科院分区：
文献类型：
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作者：
Anaya-Prado, R;Toledo-Pereyra, LH;Ward, PA
背景：中性粒细胞浸润是肝损伤伴长期低血压的特征性表现。先前的工作已经强调了中性粒细胞-内皮细胞相互作用在失血性休克后器官损伤中的重要作用。使用单克隆抗体（mab）对抗选择素或整合素受体的单阻断策略已被证明可以有效地限制这种临床疾病中观察到的组织炎症反应。一个尚未探索的话题是p -选择素和β(2)-整合素联合阻断在大鼠失血性休克后的生命炎症反应中的加性效应和潜在的抗炎特性。研究设计：体重250 ~ 300 g的Sprague-Dawley大鼠（n = 64）建立失血性休克三相模型。院前阶段包括90分钟的乳酸林格氏液液体复苏，平均动脉压（MAP）为40 mmHg；一个住院期包括60分钟的止血和乳酸林格氏液复苏，以达到80 mmHg的MAP；第三阶段为3天的观察。在最初的15分钟内，所有大鼠都有3 mL/100 g的血流量。30分钟后，75%的尾部截肢导致失血性休克失控。随机分为四组（每组16例），复苏开始时的治疗包括生理盐水（组1）；anti-P-selectin MAb, RMP-1（第二组）；aslti- β (2),-integrin MAb， WT.3（第3组）；或抗p -选择素+抗β(2)-整合素单克隆抗体（生长4）。复苏术、肝损伤试验、肝组织髓过氧化物酶和肝组织学检查。结果：p -选择素和β(2)-整合素的双重阻断显著降低了复苏所需的液体量（p < 0.05）。我们还观察到在肝损伤、肝组织髓过氧化物酶和组织学研究方面有统计学意义的改善（p < 0.05）。双阻断治疗的存活率从对照组的40%提高到60%。结论：上述结果表明，针对p -选择素和β(2)-整合素的双阻断策略对失血性休克后大鼠肝脏炎症反应具有一定的保护作用。虽然双重阻断比单独的任何一种阻断更有效，但在这种临床情况下，炎症粘附途径中可能存在冗余的问题仍然存在。[J]中华外科杂志，1998;18:22-31。(C) 1998年由美国外科医师学会发布)。
Background: Neutrophil infiltration is a characteristic feature of the hepatic injury associated with prolonged hypotension. Previous work has already stressed the important contribution of neutrophil-endothelial cell interactions in the organ injury seen after hemorrhagic shock. Single-blockade strategies using monoclonal antibodies (MAbs) against either selectin or integrin receptors have been demonstrated to be effective in limiting the tissue inflammatory response observed in this Clinical disorder. One unexplored topic is the additive effect(s) and the potential antiinflammatory properties of the combined blocking of P-selectin plus beta(2)-integrin in the lives inflammatory response after uncontrolled hemorrhagic shock in rats.Study Design: Sprague-Dawley rats (n = 64) weighing 250-300 g were included in a three-phase model of uncontrolled hemorrhagic shock. A prehospital phase consisted of 90 minutes of fluid resuscitation with lactated Ringer's solution to Peach a mean arterial pressure (MAP) of 40 mmHg; a hospital phase consisted of 60 minutes of hemostasis and fluid resuscitation with lactated Ringer's solution to reach a MAP of 80 mmHg; and the third phase was 3 days of observation. All rats had 3 mL/100 g of blood volume shed during the initial 15 minutes. At 30 minutes, 75% tail amputation produced uncontrolled hemorrhagic shock. Four groups were randomized (n = 16 per group), and treatment at the beginning of resuscitation included normal saline (group 1); anti-P-selectin MAb, RMP-1 (group 2); aslti-beta(2),-integrin MAb, WT.3 (group 3); or anti-P-selectin plus anti-beta(2)-integrin MAbs (groun 4). The folresuscitation, liver injury tests, liver tissue myeloperoxidase, and liver histology.Results: Dual blockade of P-selectin and beta(2)-integrin significantly reduced fluid requirements for resuscitation (p < 0.05). We also observed a statistically significant improvement (p < 0.05) in tests demonstrating hepatic injury, myeloperoxidase in hepatic tissue, and histology studies. Survival was increased from 40% in controls to 60% with the dual-blockade treatment.Conclusions: These results indicate that dual-blockade strategies aimed at P-selectin and beta(2)-integin provided st protective effect in the liver inflammatory response after uncontrolled hemorrhagic shock in rats. Although dual blockade was more effective than either individual blockade alone, questions remain about the possible redundancy in the inflammatory adhesion pathways after this clinical condition. (J Am Coll Surg 1998;187: 22-31. (C) 1998 by the American College of Surgeons).