| 摘要: |
| 【目的】探究槲皮素治疗猪繁殖与呼吸综合征病毒(PRRSV)诱导炎症的作用机制。【方法】将28日龄仔猪随机分为PRRSV组和PRRSV＋槲皮素低、中、高剂量组（分别在基础日粮中添加12.5，25和50 mg/kg的槲皮素），并设置空白对照组。于PRRSV感染后7，14，35 d采集血清样品，测定各组猪血清炎症因子；感染后35 d采集猪肺脏，检测肺脏组织病变；对猪血清代谢谱进行分析，筛选差异代谢物及相关代谢通路；采用网络药理学，构建槲皮素治疗炎症的“成分-靶点-通路-疾病”图。采用分子对接法验证活性成分与核心靶点的相互作用。将血清代谢组学与网络药理学联合分析，构建“靶点-代谢途径-代谢物”网络图，检测关键调控靶点磷脂酶A2(PLA2)、环氧合酶(COX)、脂氧化酶(LOX) mRNA的表达水平。【结果】与空白对照组相比，PRRSV感染7～35 d PRRSV组仔猪血清炎症因子蛋白和肺脏炎症因子mRNA均显著或极显著升高（P＜0.05或P＜0.01）；与PRRSV组相比，不同浓度槲皮素组仔猪血清炎症因子蛋白、肺脏炎症因子mRNA和PRRSV N基因的表达水平均显著或极显著降低（P＜0.05或P＜0.01）；病理组织学检测结果显示，槲皮素可改善PRRSV引起的间质性肺炎。通过代谢组学技术，从血清中筛选出16个差异代谢物，与PRRSV组相比，槲皮素能回调这些差异代谢物水平；筛选出5条关键代谢途径（甘油酯代谢、醚脂代谢、甘油磷脂代谢、酪氨酸代谢和花生四烯酸代谢）。网络药理学分析表明，槲皮素治疗间质性肺炎主要作用于EGFR、MMP9、PTGS2、CDK2和APP等靶点蛋白，与代谢通路、PI3K-Akt信号通路、IL-17信号通路和T细胞受体信号通路等密切相关。整合分析显示，甘油磷脂代谢和花生四烯酸代谢是槲皮素治疗间质性肺炎的关键代谢途径。整合分析验证结果显示，与PRRSV组相比，槲皮素组仔猪肺脏PLA2、COX1和LOX mRNA水平大多显著或极显著降低。【结论】槲皮素可通过甘油磷脂代谢和花生四烯酸代谢途径调节血清代谢物，调控炎症相关核心靶点，降低炎症水平，缓解机体代谢紊乱，发挥治疗炎症的作用。 |
| 关键词: 猪繁殖与呼吸综合征病毒 槲皮素 猪 网络药理学 代谢组学 |
| DOI：10.13207/j.jnwafu.2026.03.014 |
| 分类号: |
| 基金项目:国家自然科学基金项目（32102628）；福建省自然科学基金项目（2022J011157） |
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| Mechanism of quercetin in inhibiting PRRSV-induced inflammation in piglets based on metabolomics and network pharmacology |
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CHEN Hongbo1,2, JIANG Yuman1, LI Jiakai1, TANG Xin1, CAO Chong1, QIU Longxin1,2
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1.College of Life Science,Longyan University,Longyan,Fujian 364012,China;2.Key Laboratory of Fujian Universities Preventive Veterinary Medicine and Biotechnology,Longyan,Fujian 364012,China
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| Abstract: |
| 【Objective】The study aims to investigate the mechanism of quercetin in inhibiting porcine reproductive and respiratory syndrome virus (PRRSV)-induced inflammation.【Method】Twenty-eight-day-old piglets were randomly divided into four groups:PRRSV group,PRRSV+low-dose quercetin (12.5 mg/kg basal diet),PRRSV+medium-dose quercetin (25 mg/kg basal diet),and PRRSV+high-dose quercetin (50 mg/kg basal diet).A blank control group was also established. Serum samples were collected at 7,14,and 35 days after infection to determine serum inflammatory factors in each group.Pig lungs were collected to detect tissue lesions after 35 days of infection.The metabolic profiles of pig serum were analyzed, and the differential metabolites and related metabolic pathways were identified.A “ingredient-target-pathway-disease” diagram of inflammation for quercetin treatment was constructed by network pharmacology.The molecular docking method was used to verify the interaction between the active ingredients and the core targets.Serum metabolomics and network pharmacology were combined to construct a “target-metabolic pathway-metabolite” network diagram.The expression of key regulatory targets phospholipase A2 (PLA2),cyclooxygenase (COX),and lipoxygenase (LOX) mRNA was detected.【Result】Compared with the blank control group, piglets in the PRRSV group exhibited significant or extremely significant increases (P<0.05 or P<0.01) in serum inflammatory cytokines and pulmonary inflammatory cytokine mRNA from 7 to 35 days post-infection.In contrast,quercetin treatments at different concentrations significantly suppressed (P<0.05 or P<0.01) the expression levels of serum inflammatory cytokines,pulmonary inflammatory cytokine mRNA,and PRRSV N- gene compared to the PRRSV group.Histopathological analysis revealed that quercetin alleviated PRRSV-induced interstitial pneumonia.Through metabolomics techniques,five key metabolic pathways (glyceryl ester metabolism,ether lipid metabolism,glycerophospholipid metabolism,tyrosine metabolism,and arachidonic acid metabolism) and 16 differential metabolites in serum were identified.Compared with the PRRSV group,quercetin was able to reverse the levels of these differential metabolites.Network pharmacology analysis showed that quercetin mainly acted on target proteins such as EGFR,MMP9,PTGS2,CDK2,and APP in interstitial pneumonia treatment,which were closely linked to metabolic pathways,PI3K-Akt signaling pathways,IL-17 signaling pathways,and T cell receptor signaling pathways.Integrated analysis demonstrated glycerophospholipid metabolism and arachidonic acid metabolism as key metabolic pathways for quercetin treatment of interstitial pneumonia.The integrated verification results confirmed that the pulmonary mRNA expression levels of PLA2,COX1 and LOX in the quercetin groups were mostly significantly or extremely significantly reduced (P＜0.05 or P＜0.01) compared with the PRRSV group.【Conclusion】Quercetin can regulate serum metabolites and inflammation-related core targets through glycerophospholipid metabolism and arachidonic acid metabolism pathways,reduce inflammation levels,alleviate metabolic disorders,and play a therapeutic role in interstitial pneumonia. |
| Key words: porcine reproductive and respiratory syndrome virus quercetin pig network pharmacology metabolomics |
