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金环蛇毒液诱导的皮肤毒性的四环素保护作用。

protective effect of tetracycline against dermal toxicity induced by Jellyfish venom.

机构信息

College of Veterinary Medicine, Gyeongsang National University, Jinju, Korea.

出版信息

PLoS One. 2013;8(3):e57658. doi: 10.1371/journal.pone.0057658. Epub 2013 Mar 11.

Abstract

BACKGROUND

Previously, we have reported that most, if not all, of the Scyphozoan jellyfish venoms contain multiple components of metalloproteinases, which apparently linked to the venom toxicity. Further, it is also well known that there is a positive correlation between the inflammatory reaction of dermal tissues and their tissue metalloproteinase activity. Based on these, the use of metalloproteinase inhibitors appears to be a promising therapeutic alternative for the treatment of jellyfish envenomation.

METHODOLOGY AND PRINCIPAL FINDINGS

Tetracycline (a metalloproteinase inhibitor) has been examined for its activity to reduce or prevent the dermal toxicity induced by Nemopilema nomurai (Scyphozoa: Rhizostomeae) jellyfish venom (NnV) using in vitro and in vivo models. HaCaT (human keratinocyte) and NIH3T3 (mouse fibroblast) incubated with NnV showed decreases in cell viability, which is associated with the inductions of metalloproteinase-2 and -9. This result suggests that the use of metalloproteinase inhibitors, such as tetracycline, may prevent the jellyfish venom-mediated local tissue damage. In vivo experiments showed that comparing with NnV-alone treatment, tetracycline pre-mixed NnV demonstrated a significantly reduced progression of dermal toxicity upon the inoculation onto rabbit skin.

CONCLUSIONS/SIGNIFICANCE: It is believed that there has been no previous report on the therapeutic agent of synthetic chemical origin for the treatment of jellyfish venom-induced dermonecrosis based on understanding its mechanism of action except the use of antivenom treatment. Furthermore, the current study, for the first time, has proposed a novel mechanism-based therapeutic intervention for skin damages caused by jellyfish stings.

摘要

背景

此前,我们已经报道过,大多数(如果不是全部的话)钵水母纲水母毒液中含有多种金属蛋白酶成分,这些成分显然与毒液毒性有关。此外,众所周知,皮肤组织的炎症反应与其组织金属蛋白酶活性之间存在正相关关系。基于这些,使用金属蛋白酶抑制剂似乎是治疗水母蜇伤的一种很有前途的治疗选择。

方法和主要发现

使用体外和体内模型,研究了四环素(一种金属蛋白酶抑制剂)对减少或预防由海月水母(Scyphozoa: Rhizostomeae)毒液(NnV)引起的皮肤毒性的作用。与 NnV 孵育的 HaCaT(人角质形成细胞)和 NIH3T3(小鼠成纤维细胞)显示细胞活力下降,这与金属蛋白酶-2 和 -9 的诱导有关。这一结果表明,使用金属蛋白酶抑制剂,如四环素,可能预防水母毒液介导的局部组织损伤。体内实验表明,与单独使用 NnV 相比,四环素预先混合 NnV 显示出在接种到兔皮时皮肤毒性的进展明显减少。

结论/意义:据信,除了使用抗蛇毒血清治疗外,以前没有关于合成化学起源的治疗剂用于治疗水母毒液引起的皮肤坏死的报道,基于对其作用机制的理解。此外,目前的研究首次提出了一种基于新机制的治疗方法,用于治疗水母蜇伤引起的皮肤损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ed/3594245/54d370c89202/pone.0057658.g001.jpg

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