DNA酶I处理及中性粒细胞耗竭对小鼠急性肢体缺血再灌注损伤的影响

DNA酶I处理及中性粒细胞耗竭对小鼠急性肢体缺血再灌注损伤的影响
Effect of DNase I treatment and neutrophil depletion on acute limb ischemia-reperfusion injury in mice

Abstract
摘要
OBJECTIVE:
目的：
Extracellular traps (ETs) consisting of DNA-protein complexes formed after tissue injury contribute to the inflammatory and thrombosis cascades, thereby exacerbating injury. Exogenous DNase I has been suggested as a therapeutic strategy to limit injury in the brain and myocardium. These studies were designed to evaluate the effects of exogenous DNase I treatment on skeletal muscle injury after acute hindlimb ischemia-reperfusion (IR) injury in mice and to determine whether neutrophils are a major source of ETs in postischemic muscle tissue.
细胞外的缺陷（ETS）组成的DNA蛋白质复合物形成后组织损伤导致炎症和血栓形成的联级反应，从而加剧损伤。Exogenous DNase我已经被认为是在大脑和心肌损伤的一种治疗策略限制。这些研究的目的是评估外源DNA酶I治疗骨骼肌损伤的影响急性下肢缺血再灌注损伤（IR）小鼠和确定中性粒细胞是ETS在缺血肌肉组织的主要来源。

METHODS:
方法:
C57BL6 mice were subjected to 1.5 hours of tourniquet ischemia and 24 hours of reperfusion with and without human recombinant DNase I treatment. A separate set of mice was subjected to neutrophil depletion (ND), followed by the same intervals of IR. Laser Doppler imaging and tissue harvesting were done at 24 hours for assessment of limb perfusion, muscle fiber injury, adenosine triphosphate (ATP) level, markers of inflammation, thrombosis, and formation of ETs.
C57BL6小鼠进行1.5小时的止血带缺血和再灌注24小时没有人重组DNase I处理。一组单独的小鼠进行中性粒细胞耗竭（第二），其次是相同的时间间隔的红外光谱。激光多普勒成像和组织收集了24小时的肢体灌注评估，肌纤维损伤，三磷酸腺苷（ATP）水平、炎症、血栓形成等标记。

RESULTS:
结果:
DNase I treatment significantly reduced detection of ETs in postischemic muscle but did not alter skeletal muscle fiber injury, levels of proinflammatory molecules, or ATP level. DNase I treatment did enhance postischemic hindlimb perfusion, decreased infiltrating inflammatory cells, and reduced the expression of thrombin-antithrombin III. ND resulted in a significant yet small reduction in ETs in the postischemic muscle. ND did not alter skeletal muscle fiber injury, hindlimb perfusion, or ATP levels.
DNase I处理显著降低了ETS在缺血肌肉检测但不改变骨骼肌纤维损伤，炎性分子水平，或ATP水平。I治疗并提高缺血后肢灌注，减少炎症细胞浸润，降低凝血酶-抗凝血酶III和表达明显但小减少ETS在缺血后肌。而不改变骨骼肌纤维损伤，后肢灌注，或ATP水平。

CONCLUSIONS:
结论：
These data suggest that neither DNase I treatment nor ND was protective against IR injury, even though both decreased detection of ETs in skeletal muscle after IR. Neutrophils are not the only source of ETs after IR.
这些数据表明，无论是DNase I处理和Nd对IR损伤的保护，即使降低骨骼肌IR后ETS检测。中性粒细胞是不是IR后ETS的唯一来源。

DNA酶I处理及中性粒细胞耗竭对小鼠急性肢体缺血再灌注损伤的影响

DNA酶I处理及中性粒细胞耗竭对小鼠急性肢体缺血再灌注损伤的影响

DNA酶I处理及中性粒细胞耗竭对小鼠急性肢体缺血再灌注损伤的影响

DNA酶I处理及中性粒细胞耗竭对小鼠急性肢体缺血再灌注损伤的影响

DNA酶I处理及中性粒细胞耗竭对小鼠急性肢体缺血再灌注损伤的影响

DNA酶I处理及中性粒细胞耗竭对小鼠急性肢体缺血再灌注损伤的影响

DNA酶I处理及中性粒细胞耗竭对小鼠急性肢体缺血再灌注损伤的影响

DNA酶I处理及中性粒细胞耗竭对小鼠急性肢体缺血再灌注损伤的影响

原文：
Effect of DNase I treatment and neutrophil depletion on acute limb ischemia-repe.pdf (1.85 MB, 下载次数: 0, 售价: 99 香叶)

2016-9-26 08:18 上传

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DNA酶I处理及中性粒细胞耗竭对小鼠急性肢体缺血再灌注损伤的影响