PRS:半胱氨酸白三烯信号拮抗剂孟鲁司特不利于烧伤创面愈合

2022-09-03 MedSci原创 MedSci原创

孟鲁司特是一种半胱氨酸白三烯的拮抗剂,由美国食品和药物管理局批准用于治疗哮喘和过敏,此前被证明可以增强切除伤口的愈合和调节局部炎症。而这是否真是如此呢?

烧伤通常与伤口愈合受损有关。愈合受损是由多种因素引起的,包括在伤口部位的炎症反应失调。

孟鲁司特是一种半胱氨酸白三烯的拮抗剂,由美国食品和药物管理局批准用于治疗哮喘和过敏,此前被证明可以增强切除伤口的愈合和调节局部炎症。而这是否真是如此呢?

图1 文章来源

该研究分析了孟鲁司特和对照小鼠在烧伤后不同时间分离的烧伤创面组织的创面面积(n = 34 ~ 36)、再上皮化(n = 14)、炎症(n = 8 ~ 9)、免疫细胞浸润(n = 3 ~ 6)和增殖(n = 7 ~ 8),来研究孟鲁司特对烫伤小鼠创面愈合的影响。

图2 孟鲁司特影响烧伤愈合。

(上图)野生型小鼠遭受烧伤,并立即腹腔注射孟鲁司特或对照剂。小鼠随机分为两组。每天给老鼠拍照;代表性图片如下(上图左)。烧伤面积的量化(上图,右)

使用ImageJ采集数据,并表示为初始烧伤创面面积的百分比(n = 13 ~ 36,取决于时间点)。(下图)烧伤后第14天分离的皮肤苏木素和伊红染色切片的代表性图像(下图,左),以及再上皮化率的定量(下图,右)。黑色箭头表示创面边缘,灰色箭头表示新上皮前缘(n = 14)。数据以平均值±标准差表示。

定量聚合酶链反应分析采用Brown-Forsythe方差分析和Welch - Dunnett多重比较检验进行统计分析。伤口面积定量实验采用混合效应分析和Sidak多重比较检验进行统计分析。再上皮化实验采用双尾t检验进行统计分析(***p < 0.001;* * p < 0.01;* p < 0.05)。

但有趣的是,与之前描述的对切除创面的有益作用相反,该研究表明孟鲁司特通过损害角质细胞和内皮细胞的增殖延缓烧伤创面愈合。这在很大程度上独立于伤口部位的炎症反应,表明孟鲁司特特异性地损害了烧伤创面愈合的增殖期。不产生白三烯的小鼠的伤口愈合率不受孟鲁司特的影响。

综上述,孟鲁司特延缓烧伤创面愈合的机制主要是通过减少烧伤创面局部细胞的增殖。

虽然有必要开展临床研究来验证这一结果,但该研究建议,使用孟鲁司特的烧伤患者可能出现延迟愈合,需要额外的观察。

 

文章来源:

Nguyen Alan V,Bagood Michelle D,Wang Marilyn et al. Montelukast, an Antagonist of Cysteinyl Leukotriene Signaling, Impairs Burn Wound Healing.[J] .Plast Reconstr Surg, 2022, 150: 92e-104e.

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    2023-08-11 qindq
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    2023-01-14 kzlchina
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