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掺钕钇铝石榴石 1064 纳米激光通过 NLRP3/Caspase-1 信号通路诱导凋亡和焦亡对球形孢子丝菌的抗真菌活性:体内外研究。

Antifungal Activity of a Neodymium-Doped Yttrium Aluminum Garnet 1,064-Nanometer Laser against Sporothrix globosa by Inducing Apoptosis and Pyroptosis via the NLRP3/Caspase-1 Signaling Pathway: and Study.

机构信息

Department of Dermatology, Second Hospital of Jilin University, Changchun, Jilin, China.

Department of Dermatology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.

出版信息

Microbiol Spectr. 2021 Dec 22;9(3):e0136421. doi: 10.1128/Spectrum.01364-21. Epub 2021 Dec 15.

DOI:10.1128/Spectrum.01364-21
PMID:34908455
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8672895/
Abstract

Sporotrichosis is a deep fungal infection caused by species. Currently, itraconazole is the main treatment, but fungal resistance, adverse effects, and drug interactions remain major concerns, especially in patients with immune dysfunction. Therefore, an alternative treatment is greatly in demand. This animal study aimed to investigate the inhibitory effect of neodymium-doped yttrium aluminum garnet (Nd:YAG) 1,064-nm laser treatment on Sporothrix globosa and to explore whether it happens through regulation of the Nod-like receptor thermoprotein domain-related protein 3 (NLRP3)/caspase-1 pyroptosis and apoptosis pathway. After laser irradiation, a series of studies, including assays of viability (using the cell counting kit-8 [CCK-8]), morphological structure changes, reactive oxygen species (ROS) accumulation, mitochondrial membrane potential, oxidative stress, cell cycle progression, and metacaspase activation, were conducted to estimate the effect of Nd:YAG 1,064-nm laser treatment on Sporothrix globosa cell apoptosis . For studies, mice were infected with S. globosa and then treated with laser or itraconazole, and their footpad skin lesions and the changes in the histology of tissue samples were compared. In addition, changes in the levels of NLRP3, caspase-1, and caspase-3 were assessed by immunohistochemistry, while the levels of interleukin 17 (IL-17), interferon gamma (IFN-γ), and transforming growth factor β1 (TGF-β1) in peripheral blood were tested by enzyme-linked immunosorbent assay (ELISA). The growth of S. globosa was inhibited and apoptosis was observed after laser treatment. According to the studies, the efficacy of the laser treatment was similar to that of itraconazole. Moreover, the NLRP3/caspase-1 pyroptosis pathway was activated, with a Th1/Th17 cell response, and the expression of caspase-3 was also upregulated. Nd:YAG 1,064-nm laser treatment can effectively inhibit the growth of S. globosa by activating fungal apoptosis and pyroptosis through the NLRP3/caspase-1 pathway. Therefore, Nd:YAG 1,064-nm laser irradiation is an alternative for sporotrichosis therapy. Nd:YAG 1,064-nm laser irradiation is a useful alternative for the treatment of sporotrichosis, especially in patients with liver dysfunction, pregnant women, and children, for whom the administration of antifungal drugs is not suitable. It may improve the overall treatment effect by shortening the duration of antifungal treatment and reducing tissue inflammation.

摘要

球孢子菌病是一种由 引起的深部真菌感染。目前,伊曲康唑是主要的治疗药物,但真菌耐药性、不良反应和药物相互作用仍然是主要关注点,尤其是在免疫功能低下的患者中。因此,人们非常需要一种替代治疗方法。本动物研究旨在探讨掺钕钇铝石榴石(Nd:YAG)1064nm 激光治疗对 S. globosa 的抑制作用,并探讨其是否通过调节 Nod 样受体热蛋白结构域相关蛋白 3(NLRP3)/半胱天冬酶-1 细胞焦亡和细胞凋亡途径发生。激光照射后,通过一系列研究,包括使用细胞计数试剂盒-8(CCK-8)测定细胞活力、形态结构变化、活性氧(ROS)积累、线粒体膜电位、氧化应激、细胞周期进展和介体型半胱天冬酶激活,评估 Nd:YAG 1064nm 激光处理对 S. globosa 细胞凋亡的影响。在 研究中,用 S. globosa 感染小鼠,然后用激光或伊曲康唑治疗,比较其足底皮肤病变和组织样本的组织学变化。此外,通过免疫组织化学评估 NLRP3、半胱天冬酶-1 和半胱天冬酶-3 的水平,通过酶联免疫吸附试验(ELISA)检测外周血中白细胞介素 17(IL-17)、干扰素 γ(IFN-γ)和转化生长因子 β1(TGF-β1)的水平。激光处理后 S. globosa 的生长受到抑制并观察到细胞凋亡。根据 研究,激光治疗的疗效与伊曲康唑相似。此外,NLRP3/半胱天冬酶-1 细胞焦亡途径被激活,产生 Th1/Th17 细胞反应,半胱天冬酶-3 的表达也上调。Nd:YAG 1064nm 激光处理可通过 NLRP3/半胱天冬酶-1 途径激活真菌凋亡和细胞焦亡,有效抑制 S. globosa 的生长。因此,Nd:YAG 1064nm 激光照射是治疗球孢子菌病的一种替代方法。Nd:YAG 1064nm 激光照射是治疗球孢子菌病的一种有用方法,特别是对于肝功能不全、孕妇和儿童等不适合使用抗真菌药物的患者。它可以通过缩短抗真菌治疗的时间和减少组织炎症来提高整体治疗效果。

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