精胺酸對小鼠後肢缺血再灌流之內皮原生細胞調動及組織損傷的影響

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題名:	精胺酸對小鼠後肢缺血再灌流之內皮原生細胞調動及組織損傷的影響 Effects of arginine on the mobilization of endothelial progenitor cells and tissue injury in a mouse model of hindlimb ischemia/reperfusion
作者:	謝官俸 Hsieh, Kuan-Feng
貢獻者:	保健營養學研究所葉松鈴
關鍵詞:	精胺酸;缺血再灌流;內皮原生細胞 L-arginine;ischemia/reperfusion;endothelial progenitor cell
日期:	2016
上傳時間:	2021-11-11 16:05:43 (UTC+8)
摘要:	缺血再灌流 (ischemia/reperfusion, I/R) 常發生於嚴重肢體創傷後的醫療處置，I/R會引致大量自由基產生，引發全身性的發炎反應及器官損傷。左旋精胺酸 (L-Arginine, L-Arg) 為一氧化氮 (nitric oxide, NO) 之前驅物，NO具有清除氧自由基、抑制發炎反應且改善微循環等的作用。內皮原生細胞 (endothelial progenitor cell, EPC) 為血管修復過程中非常重要的細胞，先前研究顯示NO的介入能提升EPC調動至循環血中的數量，而I/R會造成EPC數量減少並降低I/R後血管新生與修復的功能，因此在I/R後若能提升EPC的量將對後續組織修復有很大的幫助。本實驗以C57BL/6J小鼠進行實驗，探討以靜脈注射L-Arg對後肢I/R造成之發炎反應及內皮原生細胞調動的影響。動物隨機分為5組：NC、24S、24A、48S及48A組，缺血引致之方式為使用齒顎矯正用橡皮筋綑綁於後肢大轉子上方150分鐘，造成左後肢缺血。NC組不做手術及介入，其餘4組於再灌流前以靜脈方式注射300 mg/kg body weight的saline (S) 或L-Arg (A)，並於再灌流24或48小時後犧牲。結果顯示，I/R後48小時血中EPC比例以及NO濃度降低，肌肉中keratinocyte-derived chemokine (KC) 以及monocyte chemoattractant protein (MCP)-1 mRNA基因表現量在I/R後24及48小時增加。而在L-Arg介入後血中NO及EPC比例增加，且與S組相比可提高血漿中matrix metallopeptidase-9以及vascular endothelial growth factor之濃度，而血漿中interleukin-6濃度、肌肉組織中KC以及MCP-1的基因表現量則較S組降低。本實驗結果顯示，L-Arg可能可透過提高NO的濃度增加EPC調動的功能，同時亦可降低後肢I/R所造成之發炎反應減少組織損傷。 Background: This study investigated whether administration of L-arginine (L-Arg), the precursor of nitric oxide (NO), enhances blood endothelial progenitor cell (EPC) percentages and protects against ischemia/reperfusion (I/R)-induced inflammatory response in a mouse model of hindlimb I/R injury. Methods: There were 1 normal control (NC) and 4 I/R groups. The NC group did not undergo the I/R procedure. The mice in the I/R groups were subjected to hindlimb compression with 4.5-oz orthodontic rubber bands for 150 min. Saline (S) groups were intravenously injected with saline whereas L-Arg (A) groups injected with L-Arg (300 mg/kg body weight) before reperfusion. Mice in the I/R groups were sacrificed 24 or 48 hr after reperfusion respectively. Blood and tissue samples were collected for analysis. Results: I/R led to a significantly lower blood EPC percentage, plasma NO levels and plasma interleukin-6 levels as well as the inflammatory cytokine gene expressions in muscle were elevated. Compared to the saline groups, L-Arg administration resulted in a higher EPC percentages. Also, plasma NO levels, matrix metallopeptidase-9 and vascular endothelial growth factor concentrations were upregulated whereas muscle keratinocyte-derived chemokine and monocyte chemoattractant protein-1 mRNA expressions reduced after reperfusion. Histological findings consistent with the finding that muscle injury was attenuated during I/R insult when L-Arg was administered. Conclusions: A single dose of L-Arg administration before reperfusion increases the percentage of EPCs and reduces the inflammatory reaction locally and systemically.
描述:	碩士指導教授：葉松鈴
資料類型:	thesis
顯示於類別:	[保健營養學系暨研究所] 博碩士論文

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