目的 基于网络药理学和动物实验探讨原花青素治疗青光眼的作用机制。方法 从SwissTargetPrediction、SEA、TargetNET数据库收集原花青素的作用靶点；从GeneCards、OMIM、TTD数据库收集青光眼相关靶点，通过韦恩图筛选交集靶点。利用String数据库构建蛋白相互作用（PPI）网络，CytoScape 3.9.0软件筛选Hub靶点；通过DAVID数据库进行基因本体论（GO）功能及京都基因和基因组百科全书（KEGG）富集分析；采用Autodock Vina软件进行分子对接验证。构建急性青光眼模型，设置对照组、模型组、原花青素组（50、100 mg/kg）。通过RT-PCR检测雌激素受体1（ESR1）、热休克蛋白90α家族A类成员1（HSP90AA1）、前列腺素内过氧化物合酶2（PTGS2）、B细胞淋巴瘤2（Bcl-2）、基质金属蛋白酶2（MMP2）基因表达，免疫荧光技术观察视网膜神经节细胞（RGCs）存活情况。结果 筛选得到原花青素靶点76个、青光眼相关靶点6 433个，交集关键靶点52个，Hub靶点包括ESR1、HSP90AA1、PTGS2、Bcl-2、MMP2。GO功能分析显示关键靶点涉及对外源性刺激反应、丝裂原活化蛋白激酶（MAPK）级联反应调控等生物过程；KEGG富集分析主要涉及激素信号传导、雌激素信号通路等。分子对接结果显示原花青素与Hub靶点均能稳定结合。动物实验证实，与模型组相比，原花青素组大鼠视网膜组织ESR1、Bcl-2 mRNA表达升高，HSP90AA1、PTGS2、MMP2 mRNA表达降低（P＜0.05），且RGCs存活数量显著增加（P＜0.05、0.001）。结论 原花青素可能通过调控ESR1、HSP90AA1、PTGS2、Bcl-2、MMP2等关键靶点相关通路抑制RGCs死亡，发挥治疗青光眼的作用。

Objective To explore the mechanism of action of proanthocyanidins in treatment of glaucoma based on network pharmacology and animal experiments. Methods The target sites of proanthocyanidins were collected from the SwissTargetPrediction, SEA, and TargetNET databases, the targets related to glaucoma were collected from the GeneCards, OMIM, and TTD databases, and the intersecting target sites were screened through Venn diagrams. PPI network was constructed using the String database, and the Hub target sites were screened by CytoScape 3.9.0 software. GO functional and KEGG enrichment analyses were performed using the DAVID database. Molecular docking verification was conducted using the Autodock Vina software. An acute glaucoma model was constructed, with control group, model group, and proanthocyanidins group (50 and 100 mg/kg). The expression of ESR1, HSP90AA1, PTGS2, Bcl-2, and MMP2 genes was detected by RT-PCR, and the survival status of RGCs was observed by immunofluorescence technique. Results A total of 76 proanthocyanidins targets, and 6 433 glaucoma-related targets were screened out, with 52 key intersection targets. The Hub targets included ESR1, HSP90AA1, PTGS2, Bcl-2, and MMP2. The GO function analysis showed that the key targets were involved in biological processes such as response to exogenous stimuli and regulation of MAPK cascade reaction. KEGG enrichment analysis mainly involved hormone signaling, estrogen signaling pathway, etc. The molecular docking results showed that proanthocyanidins could stably bind to the Hub targets. Animal experiments confirmed that compared with the model group, the mRNA expression of ESR1 and Bcl-2 in the rat retinal tissue increased in the anthocyanin group, while the mRNA expressions of HSP90AA1, PTGS2, and MMP2 decreased (P < 0.05), and the number of surviving RGCs significantly increased (P < 0.05, 0.001). Conclusion Proanthocyanidins may inhibit the death of RGCs by regulating key target-related pathways such as ESR1, HSP90AA1, PTGS2, Bcl-2, and MMP2, thereby exerting a therapeutic effect on glaucoma.

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河南省医学科技攻关计划项目（LHGJ20230515）；新乡市科技攻关计划项目（GG2021030）