Prolonged C1 Inhibitor Administration Improves Local Healing of Burn Wounds and Reduces Myocardial Inflammation in a Rat Burn Wound Model

Prolonged C1 Inhibitor Administration Improves Local Healing of Burn Wounds and Reduces Myocardial Inflammation in a Rat Burn Wound Model
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DOI:
10.1097/bcr.0b013e31823bc2fc
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发表时间:
2012-07-01
影响因子:
1.4
通讯作者:
Krijnen, Paul A. J.
Krijnen, Paul A. J.
中科院分区:
医学4区
文献类型:
--
作者:
Begieneman, Mark P. V.;Kubat, Bela;Krijnen, Paul A. J.

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在之前的一项研究中,作者发现烧伤创面局部持续存在急性炎症标志物,例如 C 反应蛋白和补体因子。这种持续存在的急性炎症不仅可能会延迟局部烧伤伤口的愈合,还会产生全身性影响,例如对心脏的影响。在此,我们分析了 C1 酯酶抑制剂 (C1inh)(一种补体激活抑制剂)对大鼠烧伤创面进展和心脏的影响。在雌性 Wistar 大鼠 (n = 14) 上诱导背部全层烧伤伤口 (2 x 4 cm)。将大鼠分为两组 (n = 7):对照组(仅烧伤)和 C1inh 组。 C1inh 每天静脉注射,持续 14 天。然后将烧伤伤口、后腿的健康皮肤(内部对照)和心脏固定在福尔马林中。分析组织的肉芽组织形成、上皮再生、浸润炎症细胞(粒细胞和巨噬细胞)的数量和类型以及炎症标记物(补体因子 C3 和 C4)。 C1inh治疗显着减少了肉芽组织的数量并显着增加了上皮化。 C1inh 还显着减少巨噬细胞浸润。烧伤引起巨噬细胞浸润到心室,尤其是心房。 C1inh 可以抵消这种影响。这些数据表明,C1inh 的全身治疗在不同水平上发挥作用,从而改善烧伤伤口的局部愈合并全身减少心脏炎症。因此,C1inh 可能是烧伤患者的一种可能的治疗干预措施。 (烧伤护理研究杂志 2012 年;33:544-551)
In a previous study, the authors found persistent presence of acute inflammation markers such as C-reactive protein and complement factors locally in burn wounds. This persistence of acute inflammation may not only delay local burn wound healing but also have a systemic effect, for instance on the heart. Here, the effects of C1 esterase inhibitor (C1inh), an inhibitor of complement activation, on burn wound progression and the heart were analyzed in rats. Dorsal full-thickness burn wounds (2 x 4 cm) were induced on female Wistar rats (n = 14). The rats were divided into two groups (n = 7): a control group (just burns) and a C1inh group. C1inh was administered daily intravenously for 14 days. The burn wound, healthy skin from the hind leg (internal control), and the heart were then fixed in formalin. Tissues were analyzed for granulation tissue formation, reepithelialization, amount and type of infiltrating inflammatory cells (granulocytes and macrophages), and inflammatory markers (complement factors C3 and C4). C1inh treatment significantly reduced the amount of granulation tissue and significantly increased reepithelialization. C1inh also significantly reduced macrophage infiltration. Burns induced infiltration of macrophages into the ventricles of the heart and remarkably also into the atria of the heart. This effect could be counteracted by C1inh. These data show that systemic treatment with C1inh acts at different levels resulting in improved healing locally in burn wounds and systemically reduced inflammation in the heart. Therefore, C1inh might be a possible therapeutic intervention for burn wound patients. (J Burn Care Res 2012;33:544-551)