IF=12.5！福建农林大学国家菌草工程技术研究中心： 一种新的灵芝半乳聚糖通过调节FAK-MAPK信号通路改善酒精性胃溃疡

福建农林大学国家菌草工程技术研究中心罗虹建博士和重庆三峡医学院张玉坤教授（共同第一作者），林冬梅副教授、林占熺研究员、鲁国东教授（共同通讯作者）在期刊《Carbohydrate Polymers》（IF：12.5）上发表了题为“A novel galactoglucan from Ganoderma lucidum ameliorates ethanol-induced gastric ulcers by modulating FAK-MAPK signaling pathway”的论文。

01 研究背景

胃消化性溃疡的发生主要是由于胃酸、胃酶消化和粘膜防御能力之间的失衡，导致粘膜内的自我消化。通常，胃溃疡的主要发病机制是胃粘膜屏障功能降低。幽门螺杆菌感染、饮酒、吸烟、过度使用非类固醇抗炎药(NSAIDs)以及心理或生理应激被认为是诱发GUS的最重要的危险因素。在这些因素中，高饮酒是胃粘膜损伤的最大原因。因此，本研究采用乙醇诱导的GU小鼠模型。消化性溃疡可以持续几年甚至几十年，表现为周期性发作。口服药物治疗是GUS的主要选择，如抗酸剂、质子泵抑制剂(PPI)、组胺H2受体拮抗剂等。虽然化学药物在减轻胃粘膜损伤方面有效，但它们会引起副作用，如维生素或矿物质缺乏、高胃泌素血症或心血管问题，以及长期使用后产生耐药性。因此，需要具有广泛生物活性、更好的有效性和安全轮廓的天然产品。

灵芝(Ganoderma Lucidum)，是一种担子真菌白腐菌，2000多年来在中国、日本、韩国等亚洲国家被广泛用作“长生不老的蘑菇”。先前的研究报道了灵芝及其提取物的抗炎作用和氧化应激，这表明灵芝生物活性成分可能对GUS具有药理作用。

灵芝多糖肽(GL-PP)是灵芝水提物中的主要活性成分。目前，已分离出200种类型的GL-PP，其中大部分是β-多糖，少数是α-多糖。GL-PP的生物活性与其化学结构密切相关，多糖组分的结构受生长环境、培养条件、提取方法等多种因素的影响。最新的证据表明，多糖的生物活性与其分子质量、单糖组成、连接方式、排列顺序、糖苷键类型和空间构象直接相关。因此，研究灵芝多糖组分的结构和药理活性仍具有重要意义。

02 研究方法与结论

该研究表征了一种名为GL-PPQ3的新型GL-PP，利用乙醇诱导的GU小鼠评估了其缓解GUS的效果。研究结果表明GL-PPQ3是一种超支化的半乳糖葡聚糖，其相对分子质量为41.08 kDa，主要由葡萄糖和半乳糖组成。通过甲基化、一维和二维核磁共振等综合分析确定了其结构组成，揭示了1，6-α-D-Galp、1，2，6-α-D-Galp、1，6-β-D-Glcp、1，3，6-β-D-Glcp和1，4-β-D-Glcp残基的存在。X-射线衍射仪(X射线衍射仪)显示为非晶态结构，扫描电子显微镜(SEM)显示为聚集的球形结构。机制上，GL-PPQ3通过调节FAK介导的MAPK信号通路发挥其胃保护作用。这项研究强调了GL-PPQ3作为治疗GU的潜在候选药物的潜力，为开发从天然来源提取的新型功能药物铺平了道路。

03 创新点

（1）解析出一种新型超支化半乳糖葡聚糖GL-PPQ3；

（2）GL-PPQ3在乙醇诱导的小鼠胃溃疡模型中表现出显著胃保护作用；

（3）揭示了GL-PPQ3通过调控FAK介导的MAPK信号通路发挥胃保护作用。

04 图文赏析

Fig. 1. Flowchart for the preparation of GL-PPQ3 from G. lucidum.

Fig. 2. Physicochemical properties of GL-PPQ3. A. HPGFC of profiles of GL-PPQ3. B. HPAEC of monosaccharide standards and GL-PPQ3. C. UV spectrum. D. The total ion chromatogram of PMAAs fragmentation of the derivatives from GL-PPQ3. (* denote the detected low-abundance PMAAs fragments, from left to right as follows: T-Xylp, T-Galp, 1,4-Xylp and 1,3,4-Manp).

Fig. 3. Structural characterization of GL-PPQ3 by 1D and 2D NMR in D2O solution. A. 1H NMR spectrum. B. 13C NMR spectrum. C. DEPT-135 spectrum. D. HSQC spectrum. E. COSY spectrum. F. HMBC spectrum. G. NOESY spectrum.

Fig. 4. The conformational characterization and thermal property of GL-PPQ3. A. XRD patterns. B.SEM images in the scale bar of 2000× and 50,000×. C. HPSEC-MALLS-RI chromatograms of GL-PPQ3. D. TG and DTG curves of GL-PPQ3. E. DSC curves of GL-PPQ3.

Fig. 5. GL-PPQ3 significantly reduced ulcer area and raised the pH of the gastric contents. A. Experimental schedule. B. Body weight. C. Represent images of the gastric mucosal surface. D. Ulcer area. E. pH of gastric contents. N = 6, **p < 0.01 compared with the sham group; ##p < 0.01 compared with the ethanol-treatment group.

Fig. 6. GL-PPQ3 alleviated ethanol-induced mucosal injury. A. Representative pictures of Alcain blue staining (scale bar = 100 μm). B. Gastric mucus contents. C. Representative pictures of HE staining (scale bar = 100 μm). D. Histopathological score. N = 6, **p < 0.01 compared with the sham group; ##p < 0.01 compared with the ethanol-treatment group.

Fig. 7. GL-PPQ3 ameliorated ethanol-induced inflammation and oxidative stress. A. Serum IL-1β. B. Serum TNF-α. C. Serum NO. D. Serum MDA. E. Serum GSH-px. F. Serum SOD. N = 6, **p < 0.01 compared with the sham group; ##p < 0.01 compared with the ethanol-treatment group.

Fig. 8. GL-PPQ3 suppressed ethanol-induced gastric mucosal apoptosis in a dose-dependent manner. A. Representative pictures of Tunel staining (scale bar = 100 μm). B. Tunle positive cells per field. C and D. protein expression levels of cytochrome C and caspase 3. N = 6, **p < 0.01 compared with the sham group; ##p < 0.01 compared with the ethanol-treatment group.

Fig. 9. Potential mechanisms in the pathological of ethanol-induced gastric ulcers. A. Volcano plot of differentially expressed genes. B. Bubble chart for Gene Ontology analysis. C. Heatmap of the expression levels of the top 50 differentially expressed genes. D. Potential pathological mechanisms of gastric ulcers. N = 3, p < 0.05 and fold change ≥2 were considered to be significant.

Fig. 10. GL-PPQ3 alleviates gastric ulcer via FAK-mediated MAPK and NLRP3 pathways. A and B. FAK and Akt protein expression. C and D. ERK and p38 protein expression. E and F. NLRP3 inflammasome-related proteins expression. N = 3, **p < 0.01 compared with the sham group; ##p < 0.01 compared with the ethanol-treatment group.

Fig. 11. GL-PPQ3 does not affect hepatic and kidney function during the treatment of gastric ulcers. A. Serum ALT level. B. Serum AST level. C. SCr level. D. Serum BUN level. E. Representative pictures of liver and kidney HE staining of GL-PPQ3-treated mice. N = 6, there was no significant difference among the groups.

原文链接：

https://doi.org/10.1016/j.carbpol.2025.123594