出 处:《中国中医基础医学杂志》2024年第5期821-827,共7页JOURNAL OF BASIC CHINESE MEDICINE
基 金:国家自然科学基金项目(81973912);首都卫生发展科研专项项目(首发2020-2-4183);中国中医科学院科技创新工程项目(CI2021A02602);中国中医药循证医学中心“业务研究室主任专项”(2020YJSZX-2);中国中医科学院委托项目(ZZ13-036-1)。
摘 要:目的从肠道菌群探讨固本清目方防治湿性年龄相关性黄斑变性(wet age-related macular degeneration,wAMD)小鼠的作用机制。方法105只C57 BL/6J小鼠随机分为正常组、蒸馏水组、固本清目方预防组和固本清目方治疗组,除正常组外其余小鼠均采用氢醌饲料喂养4个月联合激光光凝术诱导脉络膜新生血管(choroidal neovascularization,CNV)建立wAMD模型,并分别给予药物干预。正常组小鼠常规饲养作为对照。激光后7 d、14 d进行视网膜组织苏木素-伊红染色、脉络膜铺片、肠黏膜通透性检测和肠道菌群检测。结果与蒸馏水组比较,固本清目方预防组和固本清目方治疗组视网膜病变均减轻,其中7 d固本清目方预防组效果最明显;CNV面积均缩小,其中7 d固本清目方预防组、14 d固本清目方预防组、14 d固本清目方治疗组显著缩小(P<0.01);血清伊文思蓝浓度均降低,其中7 d固本清目方预防组显著降低(P<0.05);各组样本物种相对丰度在门和属水平上均存在差异,其中门水平上以拟杆菌门和厚壁菌门为主要优势菌群,与正常组比较,蒸馏水组厚壁菌门和拟杆菌门比值(Firmicutes/Bacteroidota,F/B)升高;与蒸馏水组比较,固本清目方预防组和固本清目方治疗组F/B值均降低。属水平分析:与正常组比较,蒸馏水组在杜氏杆菌属、梭菌属相对丰度均升高;与蒸馏水组比较,固本清目方预防组和固本清目方治疗组均出现不同程度的降低,进一步分析发现正常组、7 d固本清目方治疗组、14 d固本清目方预防组和14 d固本清目方治疗组之间均存在显著差异的生物标志物。结论固本清目方有效防治wAMD小鼠的发生、发展,其作用机制可能与增加肠道有益菌的相对丰度、重塑肠道微生态平衡、降低肠黏膜通透性有关。Objective To explore the mechanism of Guben Qingmu Fang(GBQMF)in preventing and treating wet age-related macular degeneration(wAMD)mice based on gut microbiota.Methods 105 C57 BL/6J mice were divided into normal group,distilled water group,GBQMF prevention group and GBQMF treatment group.The mice except the normal group were fed with hydroquinone(HQ)diet for 4 months,and then received laser photocoagulation(LP)to induce choroidal neovascularization(CNV)and were given corresponding drug.The normal group were fed with regular diet without HQ.Retinal hematoxylin-eosin(HE)staining,choroidal flatmount,intestinal permeability and intestinal flora were detected on days 7 and 14.Results Compared with the distilled water group,the retinopathy in GBQMF prevention group and GBQMF treatment group was alleviated on days 7 and 14,and the effect of GBQMF prevention group on day 7 was the most obvious.CNV area in GBQMF prevention group and GBQMF treatment group was smaller,and the area of CNV in GBQMF prevention group on days 7 and 14,GBQMF treatment group on day 14 reduced significantly(P<0.01).The concentration of serum evans blue(EB)in GBQMF prevention group and GBQMF treatment group was lower,and GBQMF prevention group on day 7 reduced significantly(P<0.05).The relative abundance of species in each group was different at the level of phylum and genus.At the level of phylum,Bacteroidota and Firmicutes were the dominant bacteria.Compared with the normal group,the ratio of Firmicutes/Bacteroidota(F/B)increased in the distilled water group.Compared with the distilled water group,the ratio of F/B was lower in GBQMF prevention group and GBQMF treatment group.At the level of genus,compared with the normal group,the relative abundance of Dubosiella and Clostridia_UCG-014 increased in the distilled water group.Which were lower in GBQMF prevention group and GBQMF treatment group.Further analysis revealed there were significant differences in biomarkers among the normal group,GBQMF treatment group on days 7 and 14,and GBQMF prevention
关 键 词:湿性年龄相关性黄斑变性 肠道菌群 固本清目方 肠黏膜通透性
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