肠淋巴引流可阻断创伤和失血性休克后肾脏中 5-脂氧合酶的激活。
Mesenteric lymph diversion abrogates 5-lipoxygenase activation in the kidney following trauma and hemorrhagic shock.
出版信息
J Trauma Acute Care Surg. 2014 May;76(5):1214-21. doi: 10.1097/TA.0000000000000231.
BACKGROUND
Early acute kidney injury (AKI) following trauma is associated with multiorgan failure and mortality. Leukotrienes have been implicated both in AKI and in acute lung injury. Activated 5-lipoxygenase (5-LO) colocalizes with 5-LO-activating protein (FLAP) in the first step of leukotriene production following trauma and hemorrhagic shock (T/HS). Diversion of postshock mesenteric lymph, which is rich in the 5-LO substrate of arachidonate, attenuates lung injury and decreases 5-LO/FLAP associations in the lung after T/HS. We hypothesized that mesenteric lymph diversion (MLD) will also attenuate postshock 5-LO-mediated AKI.
METHODS
Rats underwent T/HS (laparotomy, hemorrhagic shock to a mean arterial pressure of 30 mm Hg for 45 minutes, and resuscitation), and MLD was accomplished via cannulation of the mesenteric duct. Extent of kidney injury was determined via histology score and verified by urinary neutrophil gelatinase-associated lipocalin assay. Kidney sections were immunostained for 5-LO and FLAP, and colocalization was determined by fluorescence resonance energy transfer signal intensity. The end leukotriene products of 5-LO were determined in urine.
RESULTS
AKI was evident in the T/HS group by derangement in kidney tubule architecture and confirmed by neutrophil gelatinase-associated lipocalin assay, whereas MLD during T/HS preserved renal tubule morphology at a sham level. MLD during T/HS decreased the associations between 5-LO and FLAP demonstrated by fluorescence resonance energy transfer microscopy and decreased leukotriene production in urine.
CONCLUSION
5-LO and FLAP colocalize in the interstitium of the renal medulla following T/HS. MLD attenuates this phenomenon, which coincides with pathologic changes seen in tubules during kidney injury and biochemical evidence of AKI. These data suggest that gut-derived leukotriene substrate predisposes the kidney and the lung to subsequent injury.
背景
创伤后早期急性肾损伤（AKI）与多器官衰竭和死亡率有关。白三烯既与 AKI 有关，也与急性肺损伤有关。创伤和失血性休克（T/HS）后，激活的 5-脂氧合酶（5-LO）与 5-LO 激活蛋白（FLAP）在白三烯产生的第一步中在同一部位聚集。分流富含花生四烯酸 5-LO 底物的休克后肠系膜淋巴液可减轻肺损伤，并减少 T/HS 后肺中的 5-LO/FLAP 聚集。我们假设肠系膜淋巴液分流（MLD）也将减轻休克后 5-LO 介导的 AKI。
方法
大鼠进行 T/HS（剖腹术，平均动脉压降至 30mmHg 持续 45 分钟，然后复苏），并通过肠系膜导管进行 MLD。通过组织学评分确定肾损伤程度，并通过尿中性粒细胞明胶酶相关脂质运载蛋白测定验证。对肾脏切片进行 5-LO 和 FLAP 的免疫染色，并通过荧光共振能量转移信号强度确定共定位。尿液中测定 5-LO 的终白三烯产物。
结果
T/HS 组肾管状结构紊乱，出现 AKI，尿中性粒细胞明胶酶相关脂质运载蛋白测定证实，而 T/HS 期间 MLD 可使肾管状形态保持在假手术水平。T/HS 期间 MLD 减少了荧光共振能量转移显微镜显示的 5-LO 和 FLAP 之间的关联，并减少了尿液中的白三烯产生。
结论
T/HS 后，5-LO 和 FLAP 在肾髓质间质中聚集。MLD 减轻了这种现象，这与肾损伤时肾小管的病理变化和 AKI 的生化证据一致。这些数据表明，肠道来源的白三烯底物使肾脏和肺部容易受到随后的损伤。
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