Kuan-Feng Hsieh1, Juey-Ming Shih2, Yao-Ming Shih2, Man-Hui Pai3, Sung-Ling Yeh4. 1. School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan. 2. Department of Surgery, Cathay General Hospital, Taipei, Taiwan. 3. Department of Anatomy and Cell Biology, College of Medicine, Taipei Medical University, Taipei, Taiwan. 4. School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan; Nutrition Research Center, Taipei Medical University Hospital, Taipei, Taiwan. Electronic address: Sangling@tmu.edu.tw.
Abstract
OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.
OBJECTIVE: 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. METHOD: 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. RESULTS: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. CONCLUSION: 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.