他达拉非对大鼠梳状烧伤模型缺血区坏死减少的影响。

Effect of tadalafil on reduction of necrosis in the ischemic zone in a rat comb burn model.

作者信息

Singer Adam J, Towery Henry, McClain Steve A

机构信息

Department of Emergency Medicine, Stony Brook Medicine, Stony Brook, NY, United States.

出版信息

Burns. 2018 Sep;44(6):1427-1432. doi: 10.1016/j.burns.2018.05.013. Epub 2018 Jun 9.

DOI:10.1016/j.burns.2018.05.013

PMID:29895403

Abstract

OBJECTIVES

A major goal of burn management is to reduce the progression of necrosis in the zone of ischemia surrounding the central zone of necrosis. A rat comb burn model is often used to assess the progression of necrosis in the zone of ischemia. We compared various combinations of naproxen [NPX], N-acetyl cysteine [NAC], and tadalafil [TD] (a phosphodiesterase-5 inhibitor used as a vasodilator to treat erectile dysfunction) in a rat comb burn model to determine their effects on injury progression.

METHODS

We created two comb burns on the backs of 40 anesthetized Sprague-Dawley rats using a brass comb with four rectangular prongs preheated in boiling water and applied for 30s, resulting in four rectangular 10×20mm full-thickness burns separated by three 5×20mm unburned interspaces, representing the ischemic zones. We randomized five animals each to daily oral gavage with TD (1mg/kg), NPX (10mg/kg), NAC (500mg/kg), NAC+NPX, TD+NPX, TD+NAC, TD+NPX+NAC, or normal saline [NS]. Wounds were observed daily for gross evidence of necrosis in the unburned interspaces and full-thickness biopsies from the interspaces were evaluated with Hematoxylin & Eosin seven days after injury for histological evidence of necrosis.

RESULTS

The percentages of interspaces with histological evidence of necrosis at day seven were TD-40%, NPX-93%, NAC-97%, NS-87%, TD+NPX-50%, TD+NAC-40%, TD+NPX+NAC-33%, and NPX+NAC-60% (P<0.001). Repeated measures ANOVA demonstrated reduced gross percentage of interspace area undergoing necrosis in all groups that included TD, compared with all groups not including TD (P<0.001). There were no differences among the various treatments within the groups that did or did not include TD.

CONCLUSIONS

Daily oral therapy with tadalafil reduces necrosis in the unburned interspaces compared with naproxen, NAC, or their combination in a rat comb burn model. Addition of naproxen or NAC to tadalafil does not further reduce injury progression.

摘要

目的

烧伤治疗的一个主要目标是减少坏死中心区周围缺血区坏死的进展。大鼠梳状烧伤模型常被用于评估缺血区坏死的进展情况。我们在大鼠梳状烧伤模型中比较了萘普生[NPX]、N-乙酰半胱氨酸[NAC]和他达拉非[TD]（一种用作血管扩张剂治疗勃起功能障碍的磷酸二酯酶-5抑制剂）的不同组合，以确定它们对损伤进展的影响。

方法

我们使用在沸水中预热的带有四个矩形齿的黄铜梳子，在40只麻醉的Sprague-Dawley大鼠背部造成两处梳状烧伤，持续30秒，形成四个1０×20mm的矩形全层烧伤，中间由三个5×20mm未烧伤的间隙隔开，代表缺血区。我们将五只动物随机分为每日经口灌胃给予TD（1mg/kg）、NPX（10mg/kg）、NAC（500mg/kg）、NAC+NPX、TD+NPX、TD+NAC、TD+NPX+NAC或生理盐水[NS]。每天观察伤口，以寻找未烧伤间隙出现坏死的明显证据，并在损伤7天后对间隙进行全层活检，用苏木精和伊红染色评估坏死的组织学证据。

结果

在第7天，有组织学坏死证据的间隙百分比分别为：TD组-40%，NPX组-93%，NAC组-97%，NS组-87%，TD+NPX组-50%，TD+NAC组-40%，TD+NPX+NAC组-33%，NPX+NAC组-60%（P<0.001）。重复测量方差分析表明，与所有不包含TD的组相比，所有包含TD的组中，间隙区域坏死的总体百分比降低（P<0.001）。在包含或不包含TD的组内，各种治疗方法之间没有差异。