目的 应用计算生物学和动物实验研究党参水提物抗皮肤衰老的作用机制。方法 选取 50 只 SPF 级 8 周 龄 C57BL/6 小鼠随机分为 5 组，构建 D-半乳糖小鼠衰老模型，并用不同剂量党参水提物进行干预；运用苏木 精-伊红染色法（HE）和马松（Masson）染色观察小鼠皮肤组织病理变化；生化检测分析小鼠皮肤中羟脯氨酸 （HYP）、超氧化物歧化酶（SOD）和丙二醛（MDA）含量变化；利用透射电镜观察小鼠皮肤组织超微结构变化。 GEO 数据库获取皮肤老化芯片数据，筛选皮肤老化差异基因，应用 TCMSP 及 UniProt 数据库检索党参活性成 分及其药物靶点。将以上数据整合后获得党参-皮肤老化的交集靶点；通过 STRING 数据库构建党参干预皮肤 老化的核心基因蛋白互作网络。实时荧光定量 PCR（RT-qPCR）和蛋白免疫印迹验证靶点基因和其所在通路主 要蛋白在党参干预衰老模型后的表达情况。结果 与正常对照组比较，衰老模型组小鼠皮肤组织结构有明显损 伤，党参干预后明显改善了皮肤组织结构损伤；与正常对照组比较，衰老模型组小鼠皮肤组织中 HYP、SOD 含量显著减少（P＜0.05），MDA 显著升高（P＜0.05）；与衰老模型组比较，党参组 HYP、SOD 含量上升，MDA 下降，差异有统计学意义（P＜0.05）； 基质金属蛋白酶 9（MMP9）是通过计算生物学预测得到党参干预皮肤老 化的核心靶点。与正常对照组比较，衰老模型小鼠皮肤中 MMP9 的表达显著升高（P＜0.05），经党参干预后， MMP9 的表达量显著下降（P＜0.05），其所在通路 NF-κB 中的关键蛋白核因子 κB 抑制蛋白 α（IκBα）、IκB 激酶 α（IKKα）、核转录因子 κB（NF-κB）P65 的表达在党参干预后的皮肤组织中有显著变化（P＜0.05）。结论 党参 水提物可以有效减轻衰老模型小鼠皮肤组织的老化，通过抑制 NF-κB 通路中 IκBα、IKKα、NF-κB P65 蛋白 的表达，减少下游基因 MMP9 的表达，从而减轻皮肤胶原破坏，抵抗皮肤老化。

Objective To study anti-aging mechanism of skin with water extract of Codonopsis Radix by applying computational biology and animal experiments. Methods A total of 50 SPF 8-week-old C57BL/6 mice were selected and then randomly divided into five groups. D-galactose-induced aging mice model was constructed，and different doses of water extract of Codonopsis Radix were used for intervention. Hematoxylin-eosin staining （HE） and Masson staining were used to observe the pathological changes of mouse skin tissue. The content of hydroxyproline （HYP）， superoxide dismutase （SOD）， and malondialdehyde （MDA） in mouse skin were measured by biochemical detection. Transmission electron microscopy was used to observe the ultrastructural changes of mouse skin tissue. The chip data of skin aging from GEO database was obtained to screen skin-aging differential genes. TCMSP and UniProt databases were used to search for active ingredients and targets of Codonopsis Radix. The intersection of targets for Codonopsis Radix-skin aging was obtained by integrating the above data. A protein interaction network of all core gene proteins for Codonopsis Radix intervention in skin aging was constructed through the STRING database. Then，quantitative real-time PCR （RT-qPCR） and Western Blotting were used to verify target genes expression and pathway-related protein expression after the intervention of Codonopsis Radix in the aging model. Results Compared with the normal control group，the skin tissue structure of mice in senile model group were damaged significantly， the damage of skin tissue structure was improved significantly after the intervention of Codonopsis Radix. Compared with the normal control group，the content of HYP and SOD in the skin tissue of mice in senile model group were significantly reduced （P＜0.05），while MDA was significantly increased （P＜0.05）. After the intervention of Codonopsis Radix，the content of HYP and SOD were increased，while MDA was decreased （P＜0.05）.compared with senile model group. It was found that matrix metalloproteinase 9 （MMP9） was the core target for the intervention of Codonopsis Radix on skin aging in computational biology. Experiments have shown that the expression of MMP9 was significantly increased in the skin of aging model mice compared to normal control group （P＜0.05）. After the intervention of Codonopsis Radix， the expression of MMP9 is significantly reduced （P＜0.05），the expression of the key protein including inhibitory subunit of NF-kappa B alpha （IκBα）、 IκB kinase-alpha （IKKα）、nuclear factor kappa-B （NF-κB） P65 of NF-κB signaling pathway were significantly changed （P＜0.05）. Conclusion Codonopsis Radix water extract can effectively alleviate skin aging in aging model mice by inhibiting the protein expression of IκBα、IKKα、NF-κB P65 of NF-κB signaling pathway，reducing the expression of downstream gene MMP9，and ultimately alleviate skin collagen damage and resist skin aging.

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国家自然科学基金项目（82060829）；甘肃省自然科学基金（23JRRA1720）；甘肃省陇东生物资源保护利用与生态修复重点实验室开放 基金（LDSWZY2002-3）；甘肃省高校中（藏）药化学与质量研究省级重点实验室项目（zzy-2024-06）；2023年甘肃中医药大学研究生创新创业基金 （2023CX）。