Lu Qi, Xu Da-Zhong, Davidson Marson T, Haskó György, Deitch Edwin A
Department of Surgery, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA.
Crit Care Med. 2004 Dec;32(12):2464-70. doi: 10.1097/01.ccm.0000147833.51214.03.
Trauma-hemorrhagic shock is one of the leading causes of acute respiratory distress syndrome. This syndrome is associated with disruption of the alveolar barrier consisting of both epithelial and endothelial cells, which leads to a major increase in epithelial and microvascular permeability in the lungs. Although alveolar epithelial cell apoptosis has been documented as a contributing factor to this increase in permeability, it is unclear whether endothelial cell apoptosis occurs following trauma-hemorrhagic shock and, if so, the source of factors leading to this process.
Prospective animal study with concurrent control.
Small-animal laboratory.
Adult male Sprague-Dawley rats.
Trauma-hemorrhagic shock in rats was induced by laparotomy followed by blood withdrawal to achieve a mean arterial blood pressure of 30 mm Hg for 90 mins. At the end of the shock period, the rats were resuscitated, and 3 hrs later lungs were taken for histologic analysis. In other experiments, mesenteric lymph was collected from trauma-hemorrhagic shock and trauma-sham shock rats, and the biological activity of these lymph samples was tested for their ability to kill cultured endothelial cells or endothelial cells of isolated femoral veins.
Trauma-hemorrhagic shock triggered endothelial cell apoptosis in the lung as assessed using the Tunnel assay as well as by light and electron microscopic analysis. Since our previous studies have documented that mesenteric lymph is a major contributor to lung injury following shock, we also tested the hypothesis that factors in the mesenteric lymph were responsible for the endothelial cell apoptosis-inducing effect of shock. Preventing the mesenteric lymph from reaching the lung by mesenteric lymph duct ligation decreased endothelial cell apoptosis. Mesenteric lymph obtained from rats subjected to trauma-hemorrhagic shock elicited apoptosis in cultured endothelial cells and when placed into isolated femoral vein as well as increased endothelial cell monolayer permeability.
Trauma-hemorrhagic shock induces endothelial as well as epithelial cell apoptosis in the lung via factors contained in the mesenteric lymph, thereby contributing to the pathophysiology of the acute respiratory distress syndrome.
创伤失血性休克是急性呼吸窘迫综合征的主要病因之一。该综合征与由上皮细胞和内皮细胞组成的肺泡屏障破坏有关，这会导致肺部上皮和微血管通透性大幅增加。虽然肺泡上皮细胞凋亡已被证明是通透性增加的一个促成因素，但尚不清楚创伤失血性休克后内皮细胞是否会发生凋亡，如果发生，导致这一过程的因素来源是什么。
前瞻性动物研究并设同期对照。
小动物实验室。
成年雄性斯普拉格-道利大鼠。
通过剖腹术然后放血使大鼠平均动脉血压达到30毫米汞柱并维持90分钟，诱导大鼠发生创伤失血性休克。在休克期结束时，对大鼠进行复苏，3小时后取出肺组织进行组织学分析。在其他实验中，从创伤失血性休克大鼠和创伤假手术休克大鼠收集肠系膜淋巴，并检测这些淋巴样本杀死培养的内皮细胞或分离股静脉内皮细胞的生物活性。
使用Tunnel检测法以及光镜和电镜分析评估，创伤失血性休克引发了肺内内皮细胞凋亡。由于我们之前的研究表明肠系膜淋巴是休克后肺损伤的主要促成因素，我们还检验了肠系膜淋巴中的因素是休克诱导内皮细胞凋亡效应的原因这一假设。通过结扎肠系膜淋巴管防止肠系膜淋巴到达肺部，可减少内皮细胞凋亡。从创伤失血性休克大鼠获得的肠系膜淋巴可诱导培养的内皮细胞凋亡，当注入分离的股静脉时也会增加内皮细胞单层通透性。
创伤失血性休克通过肠系膜淋巴中所含的因素诱导肺内内皮细胞和上皮细胞凋亡，从而促成急性呼吸窘迫综合征的病理生理过程。
