Posttreatment with aspirin-triggered lipoxin A4 analog attenuates lipopolysaccharide-induced acute lung injury in mice:: The role of heme oxygenase-1
Posttreatment with aspirin-triggered lipoxin A4 analog attenuates lipopolysaccharide-induced acute lung injury in mice:: The role of heme oxygenase-1
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DOI：
10.1213/01.ane.0000252414.00363.c4
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发表时间：
2007-02-01
影响因子：
5.7
通讯作者：
Ye, Du-Yun
中科院分区：
文献类型：
--
作者：
Jin, Sheng-Wei;Zhang, Li;Ye, Du-Yun
背景技术背景：本研究假设15-表-16-对氯苯氧基脂氧素A4（ATL）后处理可减轻脂多糖（LPS）诱导的小鼠急性肺损伤。在假载体组中，在用生理盐水攻击后60分钟用0.9%生理盐水处理小鼠。除了施用ATL（0.7mg/kg，IV）之外，假ATL组与仓鼠-媒介物组相同，并且除了施用锌IX（ZnPP，25 mg/kg IV）之外，假ZnPP组与假媒介物组相同。在LPS-媒介物组中，小鼠在用LPS攻击后60分钟用媒介物处理。LPS-ATL组与LPS-媒介物组相同，但接受ATL。该组与LPS-ATL组相同，但在ATL前30 min给予ZnPP。结果：吸入LPS可增加支气管肺泡灌洗液中的炎性细胞计数、肿瘤坏死因子-α和蛋白浓度，并诱导肺损伤和水肿。ATL治疗后可抑制肿瘤坏死、一氧化氮和丙二醛的生成，减轻肺组织水肿、脂质过氧化反应和中性粒细胞浸润。此外，ATL促进肺组织中血红素氧合酶-1的形成。血红素氧合酶-1的活性也增加后ATL的有益效果被取消的ZnPP.CONCLUSIONS：这项研究表明，ATL后处理显着降低LPS诱导的急性肺损伤小鼠。
BACKGROUND: We hypothesized that posttreatment with 15-epi-16-parafluoro-phenoxy lipoxin A4 (ATL) could attenuate lipopolysaccharide (LPS)-induced acute lung injury in mice.METHODS: All the animals were randomly assigned to one of six groups (n = 6 per group). In the sham-vehicle group, mice were treated with 0.9% saline 60 min after they were challenged with saline. The sham-ATL group was identical to the ham-vehicle group except that ATL (0.7 mg/kg, IV) was administered, and the sham-ZnPP group was identical to the sham-vehicle group except that Zinc IX (ZnPP, 25 mg/kg IV) was administered. In the LPS-vehicle group, mice were treated with vehicle 60 min after they were challenged with LPS. LPS-ATL group was identical to the LPS-vehicle group but received ATL. The group was identical to the LPS-ATL group, but ZnPP was administered 30 min before ATL.RESULTS: Inhalation of LPS increased inflammatory cell counts, tumor necrosis factor-alpha, and protein concentration in bronchoalveolar lavage fluid and also induced lung injury and edema. Posttreatment with ATL inhibited tumor necrosis nitric oxide, and malondialdehyde production, with the outcome of decreased edema, lipid peroxidation, and the infiltration of neutrophils in lung tissues. In addition, ATL promoted the formation of heme oxygenase-1 in the lung tissues. Heme oxygenase-1 activity was also increased in the lung tissues after ATL The beneficial effects of ATL were abolished by ZnPP.CONCLUSIONS: This study demonstrates that posttreatment with ATL significantly reduces LPS-induced acute lung injury in mice.