Shireman Paula K, Contreras-Shannon Veronica, Reyes-Reyna Sara M, Robinson Susan C, McManus Linda M
South Texas Veterans Health Care System, San Antonio, TX 78229-3900, USA.
J Surg Res. 2006 Jul;134(1):145-57. doi: 10.1016/j.jss.2005.12.003. Epub 2006 Feb 20.
Monocyte chemotactic protein-1 (MCP-1) is important in macrophage recruitment and activation. However, the magnitude and temporal sequence of MCP-1 expression in relation to tissue injury and regeneration following ischemic injury remains unknown.
Hind limb ischemia was induced by femoral artery excision (FAE) in C57Bl/6J mice; a sham surgery was performed on the contralateral leg. Muscle lysates were used to measure MCP-1 and activities of creatine kinase, lactate dehydrogenase, and myeloperoxidase. Histology and immunohistochemistry were used to localize inflammation and MCP-1.
FAE resulted in a prolonged period of ischemia and the administration of MCP-1 did not alter the restoration of perfusion. One day after femoral artery excision, extensive muscle necrosis and neutrophils were prevalent throughout the musculature of the lower leg. By 3 days, a mononuclear cell infiltrate predominated in association with robust muscle regeneration as indicated by myoD expression. Concomitantly, myeloperoxidase was maximally increased. Muscle enzymes (creatine kinase and lactate dehydrogenase) were maximally decreased within 3 days and returned to baseline levels by day 14, a time course consistent with injury and regeneration observed by histology. In parallel with these inflammatory and regenerative events, MCP-1 in muscle was maximally increased at day 3. By immunohistochemistry, MCP-1 was within vascular endothelial cells and infiltrating macrophages in areas of ischemic injury.
The transient increases and selective tissue distribution of MCP-1 during early inflammation and muscle regeneration support the hypothesis that this cytokine participates in the early reparative events preceding the restoration of vascular perfusion following ischemic injury.
单核细胞趋化蛋白-1（MCP-1）在巨噬细胞募集和激活过程中起重要作用。然而，缺血性损伤后，MCP-1表达量的大小以及与组织损伤和再生相关的时间顺序仍不清楚。
通过切除C57Bl/6J小鼠的股动脉（FAE）诱导后肢缺血；对侧腿进行假手术。使用肌肉裂解物测量MCP-1以及肌酸激酶、乳酸脱氢酶和髓过氧化物酶的活性。采用组织学和免疫组织化学方法定位炎症和MCP-1。
FAE导致长时间的缺血，给予MCP-1并未改变灌注的恢复情况。股动脉切除术后1天，小腿整个肌肉组织中普遍存在广泛的肌肉坏死和中性粒细胞。到第3天，如肌原性决定因子（myoD）表达所示，单核细胞浸润占主导，同时伴有强劲的肌肉再生。与此同时，髓过氧化物酶活性最大程度增加。肌肉酶（肌酸激酶和乳酸脱氢酶）在3天内最大程度降低，并在第14天恢复到基线水平，这一病程与组织学观察到的损伤和再生情况一致。与这些炎症和再生事件同时发生的是，肌肉中的MCP-1在第3天最大程度增加。通过免疫组织化学方法发现，在缺血损伤区域，MCP-1存在于血管内皮细胞和浸润的巨噬细胞内。
在早期炎症和肌肉再生过程中，MCP-1的短暂增加和选择性组织分布支持了这样一种假说，即这种细胞因子参与了缺血性损伤后血管灌注恢复之前的早期修复事件。
