基于肠道菌群探讨小柴胡汤加味方对胃癌前病变大鼠的作用及机制OACHSSCD
Effects and Mechanisms of Modified Xiaochaihu Decoction on Precancerous Lesion of Gastric Cancer in Rats Based on Gut Microbiota
目的:探讨小柴胡汤加味方对胃癌前病变(PLGC)大鼠的干预作用,并基于肠道菌群探索其作用机制.方法:将60只大鼠采用随机数字表法均分为6组.除空白组外,其余自由饮用200 mg/L 1-甲基-3-硝基-1-亚硝基胍(MNNG)溶液,并通过饥饱失常法诱导PLGC模型,持续18周.造模成功后,空白组与模型组大鼠给予生理盐水灌胃,阳性对照组给予"叶酸片+瑞巴派特片"混悬液灌胃,低、中、高浓度小柴胡汤加味组给予相应浓度小柴胡汤加味方灌胃,持续12周.用苏木精-伊红(HE)染色观察大鼠胃黏膜病理变化;酶联免疫吸附试验(ELISA)检测血清胃蛋白酶原Ⅰ(PGⅠ)、胃蛋白酶原Ⅱ(PG Ⅱ)、胃泌素17(GAS17)、胃癌相关抗原7(MG7-Ag)、癌胚抗原(CEA)水平;用16S核糖体DNA(16S rDNA)技术检测肠道菌群变化.相关性分析采用皮尔逊(Pearson)相关法.结果:与空白组比较,模型组大鼠胃组织结构异常,黏膜层组织病变明显,部分区域呈萎缩状态且伴黏膜上皮异型,组织内可见炎症细胞浸润;小柴胡汤加味组上述病理变化减轻,血清PGⅠ、PGⅡ、GAS17、MG7-Ag、CEA水平显著改善,其肠道菌群的多样性和物种组成优化,大鼠优势菌属与PLGC大鼠血清中胃功能及肿瘤相关因子水平相关.结论:小柴胡汤加味方可能通过调节肠道菌群、影响PLGC大鼠胃功能及肿瘤相关因子表达,进而改善胃黏膜病理变化.
Objective:To investigate the interventional effects of modified Xiaochaihu Decoction on rats with precancerous lesion of gastric cancer(PLGC),and to explore its mechanisms based on gut microbiota.Methods:Sixty rats were randomly divided into six groups using a random number table method.Except for the blank group,PLGC was induced in all other groups by free access to 200 mg/L 1-methyl-3-nitro-1-nitrosoguanidine(MNNG)solution combined with an irregular feeding regimen(alternating fasting and overeating)for 18 weeks.After successful modeling,rats in the blank and model groups were administered saline by gavage,the positive control group received a suspension of folic acid tablets and rebamipide tablets,and the low-,medium-,and high-dose mod-ified Xiaochaihu Decoction groups received corresponding concentrations of the herbal formula by gavage for 12 weeks.Histopatho-logical changes in gastric mucosa were observed using hematoxylin-eosin(HE)staining.Serum levels of pepsinogen Ⅰ(PG Ⅰ),pepsinogen Ⅱ(PG Ⅱ),gastrin-17(GAS-17),MG7-Ag,and carcinoembryonic antigen(CEA)were measured by enzyme-linked im-munosorbent assay(ELISA).Gut microbiota changes were analyzed using 16S ribosomal DNA(16S rDNA)sequencing.Correlation analysis was performed using Pearson correlation analysis.Results:Compared with the blank group,rats in the model group showed abnormal gastric tissue structure,obvious mucosal lesions,partial atrophy with epithelial atypia,and inflammatory cell infiltration.These pathological changes were alleviated in the modified Xiaochaihu Decoction groups.Serum levels of PG Ⅰ,PG Ⅱ,GAS-17,MG7-Ag,and CEA were significantly improved.In addition,gut microbiota diversity and composition were optimized.Dominant bac-terial genera were correlated with serum levels of gastric function indicators and tumor-related factors in PLGC rats.Conclusion:Modified Xiaochaihu Decoction may improve gastric mucosal pathological changes by regulating gut microbiota and influencing the expression of gastric function-related and tumor-related factors in PLGC rats.
景燕燕;梅汉玮;宋云升;白湘玉;杨志鹏;袁红霞;刘军舰;袁旭
天津中医药大学,天津,301617||天津中医药大学脾胃病基础研究中心,天津,301617天津医科大学附属南开医院,天津,300100||天津中医药大学南开临床学院,天津,300100天津中医药大学,天津,301617||天津中医药大学脾胃病基础研究中心,天津,301617天津中医药大学,天津,301617||天津中医药大学脾胃病基础研究中心,天津,301617天津中医药大学,天津,301617||天津中医药大学脾胃病基础研究中心,天津,301617天津中医药大学,天津,301617||天津中医药大学脾胃病基础研究中心,天津,301617天津中医药大学脾胃病基础研究中心,天津,301617||天津医科大学附属南开医院,天津,300100||天津中医药大学南开临床学院,天津,300100内蒙古医科大学,呼和浩特,010110
医药卫生
小柴胡汤加味方胃癌前病变肠道菌群16S核糖体DNA胃功能肿瘤相关因子优势菌属
Modified Xiaochaihu DecoctionPLGCGut microbiota16S rDNAGastric functionTumor-related factorsDomi-nant bacterial genera
《世界中医药》 2026 (9)
1669-1676,8
国家自然科学基金项目(82505555,82204962)天津市教委科研计划项目(2022KJ271)天津市多元投入基金项目重点项目(21JCZDJC01150)天津市卫生健康委中医中西医结合科研课题(2025111)天津市医学重点学科建设资助项目(TJYXZDXK-3-028C).
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