Effects of L-arginine infusion during ischemia on gut blood perfusion, oxygen tension, and circulating myeloid cell activation in a murine gut ischemia/reperfusion model
Effects of L-arginine infusion during ischemia on gut blood perfusion, oxygen tension, and circulating myeloid cell activation in a murine gut ischemia/reperfusion model
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DOI：
10.1177/0148607104028004224
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发表时间：
2004-07-01
影响因子：
3.4
通讯作者：
Hiraide, H
中科院分区：
文献类型：
--
作者：
Fukatsu, K;Ueno, C;Hiraide, H
背景：肠道灌注不足被认为是严重手术损伤后早期多器官功能衰竭的一种机制。L-精氨酸（ARG）作为一氧化氮合酶的底物可以保护肠道微循环，但同时可以增强免疫细胞反应。肠缺血期间ARG输注是否改善肠缺血-再灌注（I/R）后的结局仍不清楚。方法：将癌症研究所的雄性小鼠随机分为对照组和ARG组。在IV插管后，小鼠经历90（Exp. 1)或60（实验2和3）肠I/R分钟。对照组小鼠在缺血期间以1 mL/h的速度输注生理盐水60 min，而ARG组则给予1%的盐酸ARG溶液。在Exp. 1，观察存活72小时（n = 35）。在Exp. 2、测定小肠血流量和氧分压（n = 9）。在Exp.再灌注后2 h或4 h取外周血（n = 22）。用流式细胞术检测了有或没有佛波醇肉豆蔻酸酯乙酸酯（PMA）刺激的髓样细胞产生的活性氧中间体（ROI）以及髓样细胞上CD 11 a和CD 11b的表达。结果：实验。1：存活时间无显著差异（对数秩检验，p = .2）。然而，对照组12小时的存活率为72%（13/18），ARG组为35%（6/17）（p <0.05 Fisher）。Exp. 2：ARG可明显改善缺血时肠血流灌注率，但对氧分压无明显影响。Exp.第三章：在ARG组中，在4 h时具有PMA和CD 11b表达的ROI产生高于2 h时的ROI产生，而在对照小鼠中没有显著变化。结论：ARG输注可改善缺血时肠道血液灌注，但可过度启动和激活循环髓系细胞。因此，局部缺血时静脉输注ARG会降低存活率。
Background: Gut hypoperfusion is considered to be a mechanism for early multiple-organ failure after severe surgical insults. L-Arginine (ARG) may preserve gut microcirculation as a substrate of nitric oxide synthase, but simultaneously may enhance immune cell response. It remains unknown if ARG infusion during gut ischemia improves the outcome after gut ischemia-reperfusion (I/R). Methods: Male Institute of Cancer Research mice were randomized to control and ARG groups. After IV cannulation, mice underwent 90 (Exp. 1) or 60 (Exp. 2 and 3) minutes of gut I/R. Control mice received normal saline infusion at 1 mL/h for 60 minutes during ischemia, whereas the ARG group was given 1% ARG hydrochloride solution. In Exp. 1, survival was observed for 72 hours (n = 35). In Exp. 2, blood perfusion and oxygen tension of the small intestine were measured (n = 9). In Exp. 3, peripheral blood was obtained at 2 or 4 hours after reperfusion (n = 22). Reactive oxygen intermediate (ROI) production by myeloid cells with or without phorbol myristate acetate (PMA) stimulation and expression of CD11a and CD11b on myeloid cells were examined using flow cytometry. Results: Exp. 1: There was no significant difference in survival times (log rank test, p = .2). However, survival rates at 12 hours were 72% (13/18) for the control group and 35% (6/17) for the ARG group (p < .05 Fisher). Exp. 2: ARG infusion significantly improved gut blood perfusion ratio during ischemia but had no effect on oxygen tension. Exp. 3: In the ARG group, ROI production with PMA and CD11b expression at 4 hours were higher than those at 2 hours, whereas there were no significant changes in the control mice. Conclusions: ARG infusion improves intestinal blood perfusion during ischemia but primes and activates circulating myeloid cells excessively. Consequently, IV infusion of ARG during ischemia reduces survival rate.