Modulation of inflammation by reactive oxygen species: Implications for aging and tissue repair

Modulation of inflammation by reactive oxygen species: Implications for aging and tissue repair
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DOI:
10.1016/s0891-5849(00)00378-6
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发表时间:
2001-01-01
影响因子:
7.4
通讯作者:
Khalil, Z
Khalil, Z
中科院分区:
医学1区
文献类型:
--
作者:
Khodr, B;Khalil, Z

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组织损伤后,足够的炎症血管反应对于随后的组织修复至关重要。本研究的目的是研究活性氧(ROS,在损伤部位产生)在调节急性和慢性损伤条件下炎症反应中的作用。研究了年龄的影响以及这种调节对组织修复的影响。使用激光多普勒血流计,监测麻醉大鼠后足垫真空诱导水泡底部的炎症血管反应(65 mg/kg Nembutal)。 P 物质 (SP) 灌注到水疱基底上会加剧炎症。在幼稚皮肤(急性损伤模型)或慢性损伤神经支配的皮肤(慢性损伤模型)上诱发的急性水疱中检查炎症反应。此外,在水疱诱导后的早期和晚期、0 和 5 小时检查急性损伤模型。分别。通过在急性损伤的水疱基底上联合灌注抗氧化剂:超氧化物歧化酶和过氧化氢酶,或在慢性损伤的大鼠中肌肉注射替拉扎德来评估ROS的参与情况。结果表明,抗氧化治疗对幼鼠急性炎症早期和晚期的反应没有影响。然而,在老年大鼠中,在急性炎症的早期和晚期,血管反应分别显着减弱(60%)或显着增加(40%)。在慢性损伤条件下,抗氧化治疗显着增强了年轻和年老大鼠的反应。然后我们检查了抗氧化剂的效果。 tirilazad,对大鼠肩胛内区域(使用 CO2 激光)诱导的全层热损伤的愈合。烧伤后,从第 1 天(早期治疗)或第 6 天(晚期治疗)开始在伤口部位周围注射替拉扎德。与老年对照组(20.3 +/- 0.8 天)相比,替拉扎德对伤口闭合有相反的作用,早期和晚期治疗延迟(24.6 +/- 0.6 d)或加速(14.2 +/- 0.3 d)伤口闭合。结果表明,ROS 具有矛盾的作用,随着年龄的增长,对炎症反应产生积极或消极的影响。我们认为,在设计加速组织修复的治疗方案时,应考虑活性氧在调节炎症中的作用。 (C) 2000 爱思唯尔科学公司。
Following tissue injury, adequate inflammatory vascular responses are essential for subsequent tissue repair. The aims of this study were to investigate the role of reactive oxygen species (ROS, generated at the injury site) in modulating the inflammatory response under acute- and chronic-injury conditions. The effect of age and the implications of this modulation for tissue repair was investigated. Using laser Doppler flowmetry, inflammatory vascular responses were monitored in the base of vacuum-induced blisters in the hind footpad of anesthetized rats (65 mg/kg Nembutal). Inflammation was amplified by superfusion of substance P (SP) over the blister base. The inflammatory response was examined in acute blisters induced on either naive skin (acute-injury model) or on skin innervated by a chronically injured nerve (chronic-injury model). Furthermore, the acute-injury model was examined during early and late phases, 0 and 5 h after blister induction. respectively. The involvement of ROS was assessed by either combined superfusion of the antioxidants: superoxide dismutase and catalase over the blister base in acute-injury, or intramuscular injection of tirilazad in chronically injured rats. The results showed that antioxidant treatment had no effect on the response during early and late phases of acute inflammation in young rats. However in old rats, the vascular response was significantly attenuated (60%) or significantly increased (40%) during the early and late phases of acute inflammation, respectively. Under chronic-injury conditions, antioxidant treatment significantly enhanced the response in both young and old rats. We then examined the effect of antioxidant. tirilazad, on the healing of a full thickness thermal injury induced in the intrascapular region (using a CO2 laser) of the rat. Following burn injury, tirilazad was injected around the wound site starting on day 1 (early treatment) or day 6 (late treatment). Tirilazad had opposing actions on wound closure with early and late treatments delaying (24.6 +/- 0.6 d) or accelerating (14.2 +/- 0.3 d) wound closure compared with the group of aged controls (20.3 +/- 0.8 d). The results suggest that ROS have a paradoxical role exerting either a positive or negative effect on the inflammatory response with age. We contend that the role of ROS in modulating inflammation should be considered when designing treatment protocols to accelerate tissue repair. (C) 2000 Elsevier Science Inc.