School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan.
Department of Surgery, Cathay General Hospital, Taipei, Taiwan.
Nutrition. 2018 Nov;55-56:29-35. doi: 10.1016/j.nut.2018.02.019. Epub 2018 Mar 27.
This study investigated whether the administration of L-Arginine, the precursor of nitric oxide, increases the percentages of blood endothelial progenitor cells and protects against ischemia/reperfusion induced inflammatory response in a mouse model of hind-limb IR injury.
C57BL/6 mice were randomized to one normal-control and four ischemia/reperfusion groups. The normal-control group did not undergo an ischemia/reperfusion procedure but mice in the ischemia/reperfusion groups were subjected to 150 min of unilateral hind-limb ischemia. The ischemia/reperfusion groups were subjected to either intravenous saline or L-Arginine (300 mg/kg body weight) administration before reperfusion and then sacrificed at either 24 h or 48 h after reperfusion. Blood and muscle tissues were collected for analysis.
Ischemia/reperfusion injury led to a significant decrease in the percentage of blood endothelial progenitor cells and plasma nitric oxide concentration but plasma interleukin-6 levels and gene expression of inflammatory cytokines in injured muscle tissue were elevated. In contrast to the saline groups, those with L-Arginine administration were able to maintain a normal level of blood endothelial progenitor cells. In addition, after reperfusion, concentrations of nitric oxide, matrix metallopeptidase-9, and vascular endothelial growth factor in plasma were upregulated but keratinocyte-derived chemokine and monocyte chemoattractant protein-1 messenger RNA expressions in muscle were attenuated 48 h after reperfusion. Histologic findings also demonstrated a significant reduction of ischemia/reperfusion-induced muscle injury when L-Arginine was administered.
A single dose of L-Arginine administration before reperfusion increases the percentage of endothelial progenitor cells and reduces the inflammatory reaction locally and systemically after ischemia/reperfusion injury.
本研究旨在探讨在小鼠后肢 IR 损伤模型中，给予一氧化氮前体 L-精氨酸是否会增加血液内皮祖细胞的百分比并防止缺血/再灌注引起的炎症反应。
将 C57BL/6 小鼠随机分为正常对照组和 4 个缺血/再灌注组。正常对照组不进行缺血/再灌注操作，但缺血/再灌注组的小鼠进行单侧后肢缺血 150 分钟。缺血/再灌注组在再灌注前给予静脉注射生理盐水或 L-精氨酸（300mg/kg 体重），然后在再灌注后 24 小时或 48 小时处死。采集血液和肌肉组织进行分析。
缺血/再灌注损伤导致血液内皮祖细胞的百分比和血浆一氧化氮浓度显著下降，但损伤肌肉组织中血浆白细胞介素-6 水平和炎症细胞因子的基因表达升高。与生理盐水组相比，给予 L-精氨酸组能够维持正常的血液内皮祖细胞水平。此外，再灌注后，血浆中一氧化氮、基质金属蛋白酶-9 和血管内皮生长因子的浓度升高，但肌肉中角质细胞衍生趋化因子和单核细胞趋化蛋白-1 信使 RNA 的表达在再灌注后 48 小时减弱。组织学发现，给予 L-精氨酸后，缺血/再灌注引起的肌肉损伤显著减少。
在再灌注前给予单次剂量的 L-精氨酸可增加内皮祖细胞的百分比，并减少缺血/再灌注损伤后局部和全身的炎症反应。
