目的 基于NOD样受体热蛋白结构域3（NOD like receptor family pyrin domain containing 3，NLRP3）炎症小体通路探讨香茅醇对耐甲氧西林金黄色葡萄球菌（methicillin-resistant Staphylococcus aureus，MRSA）诱导小鼠皮肤感染的治疗作用及相关机制。方法 采用微量肉汤稀释法测定香茅醇对标准MRSA菌株的最低抑菌浓度（minimum inhibitory concentration，MIC）；建立C57BL/6雌性小鼠背部全层皮肤MRSA感染模型，设置对照组、模型组、阳性对照（2%莫匹罗星）组和香茅醇低、中、高剂量（0.75%、1.50%、3.00%香茅醇凝胶）组，局部给药7 d。动态检测伤口愈合率，苏木素-伊红（hematoxylin-eosin，HE）染色观察皮肤组织病理变化，ELISA法检测皮肤组织中白细胞介素-1β（interleukin-1β，IL-1β）、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、超氧化物歧化酶（superoxide dismutase，SOD）和丙二醛（malondialdehyde，MDA）水平，Masson染色观察皮肤组织胶原纤维沉积；通过RNA-seq转录组测序、qRT-PCR及Western blotting检测皮肤组织中NLRP3炎症小体通路相关基因及蛋白表达，分子对接预测香茅醇与相关炎症靶点的结合能力。乳酸脱氢酶（lactate dehydrogenase，LDH）释放实验检测香茅醇对MRSA感染的人永生化角质形成细胞焦亡的影响。结果 香茅醇对MRSA具有显著的抗菌活性，MIC为0.312 5～0.625 0 mg/mL。体内实验中，与模型组比较，香茅醇能显著加快伤口愈合，减轻炎症细胞浸润及组织水肿，降低皮肤组织IL-1β、TNF-α水平（P＜0.05、0.01、0.001），显著增加伤口部位胶原纤维沉积（P＜0.05、0.01），并抑制NLRP3炎症小体-细胞焦亡通路激活（P＜0.05、0.01、0.001）。分子对接结果显示，香茅醇可与IL-1β等靶蛋白结合。体外实验中，香茅醇显著抑制MRSA感染的HaCaT细胞LDH释放（P＜0.05、0.01）。结论 香茅醇对MRSA诱导的小鼠皮肤感染具有显著的抗菌、抗炎及促修复作用，其机制可能与抑制NLRP3炎症小体-细胞焦亡通路、减少促炎细胞因子释放、改善局部免疫微环境及促进胶原沉积相关。

Objective To explore the therapeutic effect and related mechanism of citronellol on methicillin-resistant Staphylococcus aureus (MRSA)-induced skin infections in mice via NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome pathway. Methods The minimum inhibitory concentration (MIC) of citronellol against standard MRSA strains was determined using the microbroth dilution method. A full-thickness skin MRSA infection model was established in female C57BL/6 mice, control group, model group, positive control (2% mupirocin) group, citronellol low-, medium- and high-dose (0.75%, 1.50%, 3.00% citronellol gel) groups were set up. Local administration was performed for 7 d. Wound healing rates were dynamically monitored, hematoxylin-eosin (HE) staining was used to observe histopathological changes in skin tissues, and ELISA was used to detect levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD) and malondialdehyde (MDA) in skin tissues. Masson staining was used to observe collagen fiber deposition in skin tissues. RNA-seq transcriptome sequencing, qRT-PCR and Western blotting were employed to analyze the expressions of NLRP3 inflammasome pathway-related genes and proteins in skin tissues, while molecular docking was used to predict the binding affinity of citronellol to relevant inflammatory targets. The lactate dehydrogenase (LDH) release assay was used to evaluate the effect of citronellol on pyroptosis in MRSA-infected immortalized keratinocytes. Results Citronellol exhibited significant antibacterial activity against MRSA, with an MIC ranging from 0.312 5—0.625 0 mg/mL. In vivo experiments revealed that compared with model group, citronellol significantly accelerated wound healing, reduced inflammatory cell infiltration and tissue edema, decreased IL-1β and TNF-α levels in skin tissues (P < 0.05, 0.01, 0.001), markedly increased collagen fiber deposition at wound sites (P < 0.05, 0.01), and inhibited the activation of NLRP3 inflammasome-cell pyroptosis pathway (P < 0.05, 0.01, 0.001). Molecular docking results indicated that citronellol could bind to target proteins such as IL-1β. In vitro experiments demonstrated that citronellol significantly suppressed LDH release in MRSA-infected HaCaT cells (P < 0.05, 0.01). Conclusion Citronellol exerts significant antibacterial, anti-inflammatory and wound repair-promoting effects on MRSA-induced skin infections in mice. Its mechanism may be related to inhibiting NLRP3 inflammasome-cell pyroptosis pathway, reducing the release of pro-inflammatory cytokines, improving the local immune microenvironment, and promoting collagen deposition.

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国家自然科学基金资助项目（82204601）；国家自然科学基金资助项目（82472328）；四川省重点研发计划项目（2024YFFK0090）；“成医英才”登峰计划人才项目（2024qnGzn14）；临床科学研究基金资助项目（2024GJQY23，24LHBBYY1-04，23LHPDZYB21）