Mechanisms of toxic smoke inhalation and burn injury: role of neutral endopeptidase and vascular leakage in mice.
Mechanisms of toxic smoke inhalation and burn injury: role of neutral endopeptidase and vascular leakage in mice.
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DOI：
10.1080/15376510902725649
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发表时间：
2009-03
影响因子：
3.2
通讯作者：
Hawkins HK
中科院分区：
文献类型：
--
作者：
Jacob S;Deyo DJ;Cox RA;Traber DL;Herndon DN;Hawkins HK
使用新开发的烟雾和烧伤（SB）损伤小鼠模型研究了中性肽链内切酶（NEP）对肺部急性炎症的影响。 C57BL/6 小鼠接受静脉注射预处理。在 SB 损伤前 1 小时给予特定 NEP 拮抗剂 CGS-24592 (10 mg/Kg) 剂量（n = 5-8/组）。小鼠通过腹膜内注射麻醉。氯胺酮/甲苯噻嗪，插管，并暴露于冷却的棉烟中（2 × 30 s）。 s.c.之后注射1毫升0.9%生理盐水，每人接受40%总体表面积（TBSA）火焰烧伤。腹膜内给予丁丙诺芬 (2 mg/kg)。并用生理盐水复苏。静脉注射伊文思蓝染料 (EB)牺牲前 15 分钟。测量肺湿/干重比。血管灌注后，分析肺部的 EB 染料和髓过氧化物酶 (MPO) 水平。在用 CGS-24592 预处理并随后进行 SB 损伤的小鼠中，EB 水平显着高于仅进行 SB 损伤的小鼠（61%，p = 0.043）。与假手术相比，仅 SB 损伤的动物中 EB 染料显着增加（144%，p = 0.035）。与仅 SB 损伤的动物相比，在 SB 损伤前用 CGS-24592 预处理的小鼠中，湿重/干重比显着较高 (27%，p = 0.042)。与仅 SB 损伤的小鼠相比，CGS-24592 预处理还导致 MPO 显着增加（29%，p = 0.026）。总之，当前的研究表明，特定的 NEP 抑制剂 CGS 24592 会加剧 SB 诱导的小鼠肺损伤和炎症。
The effects of neutral endopeptidase (NEP) in acute inflammation in the lung were studied using a newly developed murine model of smoke and burn (SB) injury. C57BL/6 mice were pretreated with an i.v. dose of a specific NEP antagonist CGS-24592 (10 mg/Kg) 1 h prior to SB injury (n = 5–8/group). Mice were anesthetized with i.p. ketamine/xylazine, intubated, and exposed to cooled cotton smoke (2 × 30 s). After s.c. injection of 1 ml 0.9% saline, each received a 40% total body surface area (TBSA) flame burn. Buprenorphene (2 mg/kg) was given i.p. and resuscitated by saline. Evans Blue dye (EB) was injected i.v. 15 min before sacrifice. Lung wet/dry weight ratio was measured. After vascular perfusion, lungs were analyzed for their levels of EB dye and myeloperoxidase (MPO). In mice pretreated with CGS-24592 followed by SB injury the EB levels were significantly higher (61%, p = 0.043) than those with SB injury alone. There was a significant increase (144%, p = 0.035) in EB dye in animals with SB injury alone as compared to shams. In mice pretreated with CGS-24592 prior to SB injury wet/dry weight ratios were significantly (27%, p = 0.042) higher compared to animals with SB injury alone. CGS-24592 pretreatment also caused a significant increase in MPO (29%, p = 0.026) as compared to mice with SB injury alone. In conclusion the current study indicates that specific NEP inhibitor CGS 24592 exacerbates the SB-induced lung injury and inflammation in mice.
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影响因子：
3.3
作者：
BARROW, RE;MORRIS, SE;HERNDON, DN
通讯作者：
HERNDON, DN
影响因子：
3.6
作者：
Nicolau, M;Dovichi, SS;Cuttle, G
通讯作者：
Cuttle, G
影响因子：
120.7
作者：
CRAPO, RO
通讯作者：
CRAPO, RO
影响因子：
2.2
作者：
Day, AL;Wick, E;Kirkwood, KS
通讯作者：
Kirkwood, KS
影响因子：
10.4
作者：
Lee, LY;Widdicombe, JG
通讯作者：
Widdicombe, JG