[关键词]
[摘要]
目的 比较白矾及其不同炮制品[枯矾、蜂巢煅制白矾(蜡矾)]对急性胃溃疡小鼠的治疗作用,优选最佳炮制方法,并借助代谢组学技术揭示其潜在机制。方法 采用乙醇诱导急性胃溃疡小鼠模型,通过胃溃疡指数、胃组织病理学染色、氧化应激指标、炎症因子及黏膜修复因子评估药效;采用非靶向代谢组学分析白矾及其不同炮制品治疗急性胃溃疡的潜在作用机制。结果 模型组小鼠胃黏膜呈现大面积出血性糜烂,各给药组胃溃疡评分、胃溃疡指数均显著降低(P<0.05、0.01、0.001),溃疡抑制率排序由高到低为蜡矾>白矾>枯矾。胃组织病理学染色结果表明,各给药组均能减轻胃黏膜损伤,炎症细胞浸润、胶原纤维降解较模型组减少,糖蛋白含量较模型组升高,其中蜡矾组效果最佳。与模型组比较,各给药组均能显著提高血清中超氧化物歧化酶(superoxide dismutase,SOD)活性(P<0.01、0.001),降低血清中丙二醛(malondialdehyde,MDA)、白细胞介素-6(interleukin-6,IL-6)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平(P<0.01、0.001),上调胃组织中表皮生长因子(epidermal growth factor,EGF)和碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)的表达(P<0.01、0.001),下调胃组织中IL-1β、IL-6和TNF-α的表达(P<0.01、0.001)。代谢组学分析揭示了白矾和蜡矾在调节α-亚麻酸代谢、牛磺酸和亚牛磺酸代谢、卟啉和叶绿素代谢、类固醇生物合成以及D-精氨酸和D-鸟氨酸代谢等关键代谢途径中的作用,其中蜡矾的代谢特征与黏膜保护和氧化应激缓解的相关性最强。结论 白矾及其不同炮制品对急性胃溃疡均有疗效,其中蜡矾组综合效果最佳,表明古法炮制可增强白矾药效。白矾和蜡矾可调节α-亚麻酸代谢、牛磺酸代谢等关键途径,蜡矾的代谢特征与黏膜保护和氧化应激缓解相关性最强,可能通过抗氧化、抗炎及促进黏膜修复发挥疗效。
[Key word]
[Abstract]
Objective To compare the therapeutic effects of Baifan (Alumen) and its different processed products (calcined Alumen, honeycomb calcined Alumen) on mice with acute gastric ulcer, and select the optimal processing method, reveal its potential mechanism through metabolomics technology.Methods Ethanol-induced acute gastric ulcer mouse model was used, and the efficacy was evaluated by gastric ulcer index, gastric histopathological staining, oxidative stress index, inflammatory factors and mucosal repair factors. Non targeted metabolomics was used to analyze the potential mechanisms of Alumen and its different processed products in the treatment of acute gastric ulcers.Results The model group showed extensive hemorrhagic erosion of gastric mucosa, and the gastric ulcer score and index of each treatment group were significantly reduced (P < 0.05, 0.01, 0.001). The ulcer inhibition rate was ranked from high to low as honeycomb calcined Alumen > Alumen > calcined Alumen. The pathological staining results of gastric tissue showed that all treatment groups were able to alleviate gastric mucosal damage, reduce inflammatory cell infiltration and collagen fiber degradation compared to model group, and increase glycoprotein content compared to model group, with honeycomb calcined Alumen group showing the best effect. Compared with model group, all treatment groups were able to significantly increase the activity of superoxide dismutase (SOD) in serum (P < 0.01, 0.001), reduce the levels of malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in serum (P < 0.01, 0.001), up-regulate the expressions of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) in gastric tissue (P < 0.01, 0.001), and down-regulate the expressions of IL-1β, IL-6 and TNF-α in gastric tissue (P < 0.01, 0.001). Metabolomics analysis revealed the effects of Alumen and honeycomb calcined Alumen on regulating key metabolic pathways such as α-linolenic acid metabolism, taurine and hypotaurine metabolism, porphyrin and chlorophyll metabolism, steroid biosynthesis, and D-arginine and D-ornithine metabolism. Among them, the metabolic characteristics of honeycomb calcined Alumen showed the strongest correlation with mucosal protection and oxidative stress relief.Conclusion Alumen and its different processed products have therapeutic effects on acute gastric ulcers, among which honeycomb calcined Alumen group has the best comprehensive effect, indicating that ancient processing can enhance the efficacy of Alumen.Alumen and honeycomb calcined Alumen can regulate key pathways such as α-linolenic acid metabolism and taurine metabolism. The metabolic characteristics of honeycomb calcined Alumen are most strongly correlated with mucosal protection and oxidative stress relief, and may exert therapeutic effects through antioxidant, anti-inflammatory and promotion of mucosal repair.
[中图分类号]
R285.5
[基金项目]
吉林省自然科学基金资助项目(YDZJ202501ZYTS271)