The role of lymph factors in lung injury, bone marrow suppression, and endothelial cell dysfunction in a primate model of trauma-hemorrhagic shock
The role of lymph factors in lung injury, bone marrow suppression, and endothelial cell dysfunction in a primate model of trauma-hemorrhagic shock
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DOI：
10.1097/01.shk.0000133592.55400.83
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发表时间：
2004-09-01
期刊：
影响因子：
3.1
通讯作者：
Redl, H
中科院分区：
文献类型：
--
作者：
Deitch, EA;Forsythe, R;Redl, H
对创伤失血性休克(T/HS)啮齿动物模型的研究表明，肠道淋巴中含有的因子与急性肺损伤和骨髓抑制有关，并有助于全身炎症状态。由于在啮齿动物T/HS模型中观察到的结果可能不能完全反映受伤患者的反应，因此在对人类进行侵入性研究之前，有必要确定这些结果是否可以在灵长类动物身上复制。因此，本研究的三个目标是确定胸腔导管淋巴分流是否能减少T/HS所致的肺损伤；比较T/HS和创伤假休克(T/SS)状态下狒狒胸腔导管淋巴的生物活性；以及比较T/SS、T/HS和T/HS状态下与胸管淋巴引流状态下的血浆的生物活性和组成。实验分三组：T/SS+胸腔导管淋巴转移组、T/HS组和T/HS+淋巴转移组(T/HS-LD组)。创伤部分包括颈淋巴清扫术和锁骨近端切除加剖腹手术。Hs维持在平均动脉压40 mm Hg，维持在40 mm Hg，直到基础过量达到-5mEq或总休克时间达到3h。分别于休克期前、休克期中、休克期结束后、休克期结束时、休克期结束时、休克胸导管淋巴分流可预防T/HS所致肺损伤(T/SS=4.6+/-0.5；T/HS+LD=4.8+/-0.7；T/HS=5.4+/-0.6；P<0.05)。休克早期采集的T/HS组淋巴对人内皮细胞有细胞毒作用(HUVECs在T/SS淋巴中的存活率为16%比100%)，并使HUVEC单层通透性增加近2倍(P<；0.01)。T/HS淋巴和血浆对人骨髓的红细胞(红系祖细胞)和白细胞(粒-单核细胞集落形成单位)的增殖抑制作用接近对照组的50%，而T/SS淋巴和血浆不抑制人骨髓祖细胞的生长(P<；0.05)。两组T/HS患者血浆细胞因子水平均有不同程度升高。因此，在T/HS的灵长类动物模型中，淋巴中携带的肠源性因子加剧了肺损伤和内皮功能障碍，并抑制了骨髓前体细胞的生长。
Studies in rodent models of trauma-hemorrhagic shock (T/HS) have shown that factors contained in the intestinal lymph are responsible for acute lung injury and bone marrow suppression, and that they contribute to a systemic inflammatory state. Because results observed in rodent T/HS models may not fully reflect the response of injured patients, it is necessary to determine if these results can be replicated in primates before the institution of invasive studies in humans. Thus, the three goals of this study were to determine if diversion of thoracic duct lymph reduced T/HS-induced lung injury; to compare the biologic activity of thoracic duct lymph from baboons subjected to T/HS or trauma sham-shock (T/SS); and to compare the biologic activity and composition of plasma from baboons subjected to T/SS, T/HS, and T/HS with thoracic duct lymph drainage. Three groups of baboons were studied: T/SS plus lymph diversion via a thoracic duct catheter, T/HS, and T/HS plus lymph diversion (T/HS-LD). The trauma component consisted of a neck dissection with resection of the proximal clavicle plus a laparotomy. HS was to a mean arterial pressure of 40 mmHg and was maintained at 40 mmHg until the base excess reached -5 mEq or the total shock period reached 3 h. Volume resuscitation was carried out by reinfusing the shed blood plus crystalloids. Before, during, and after the T/HS or T/SS period, blood and lymph samples were obtained for analysis, and lung samples were harvested for measurement of lung wet-to-dry ratio at 5 h after the end of the shock period. Diversion of thoracic duct lymph prevented T/HS-induced lung injury as reflected in lung wet-to-dry weight ratios (T/SS = 4.6 +/- 0.5; T/HS+LD = 4.8 +/- 0.7; T/HS = 5.4 +/- 0.6; P < 0.05). Lymph from the T/HS group collected during the early postshock period was cytotoxic for human endothelial cells (HUVECs; 16% vs. 100% survival in T/SS lymph) and increased HUVEC monolayer permeability almost 2-fold (P < 0.01). T/HS lymph and plasma also suppressed red blood cell (erythroid burst-forming unit) and white blood cell (granulocyte-monocyte colony-forming unit) progenitor cell growth of human bone marrow to similar to50% of control, whereas T/SS lymph and plasma were not suppressive (P < 0.05). Plasma cytokine levels were increased to a similar degree in the two T/HS groups. Thus, in a primate model of T/HS, gut-derived factors carried in the lymph potentiates lung injury and endothelial dysfunction, and suppresses bone marrow progenitor cell growth.