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1.山西医药学院:,医学检验系,山西汾阳
2.山西医药学院:,科技中心,山西汾阳
付 慧,E-mail: fuhui132@163.com
收稿:2025-12-11,
修回:2026-01-05,
录用:2026-01-06,
纸质出版:2026-01-30
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付慧,徐本锦,卫宇阳,等.人参皂苷Rb1通过调节肠-肝轴改善非酒精性脂肪性肝炎的作用及机制研究[J].陆军军医大学学报,2026,48(02):158-168.DOI:10.16016/j.2097-0927.202512059.
FU H,XU B J,WEI Y Y,et al.Effects and underlying mechanisms of ginsenoside Rb1 in improving non-alcoholic steatohepatitis via modulation of the gut-liver axis[J].J Army Med Univ,2026,48(02):158-168.DOI:10.16016/j.2097-0927.202512059.
付慧,徐本锦,卫宇阳,等.人参皂苷Rb1通过调节肠-肝轴改善非酒精性脂肪性肝炎的作用及机制研究[J].陆军军医大学学报,2026,48(02):158-168.DOI:10.16016/j.2097-0927.202512059. DOI:
FU H,XU B J,WEI Y Y,et al.Effects and underlying mechanisms of ginsenoside Rb1 in improving non-alcoholic steatohepatitis via modulation of the gut-liver axis[J].J Army Med Univ,2026,48(02):158-168.DOI:10.16016/j.2097-0927.202512059. DOI:
目的
2
探讨人参皂苷Rb1对非酒精性脂肪性肝炎(non-alcoholic steatohepatitis, NASH)的治疗作用及其通过调节肠道菌群、修复肠屏障改善肝脏炎症和代谢紊乱的机制。
方法
2
建立高脂高胆固醇饮食(high-fat, high-cholesterol diet, HFHCD)诱导的NASH小鼠模型,并给予Rb1腹腔注射干预;构建油酸+胆固醇诱导的HepG2细胞NASH模型进行验证。采用血清生化、组织病理(HE、Oil Red O、Masson、天狼星红染色)、Western blot检测炎症及紧密连接蛋白表达;16S rRNA基因测序分析肠道菌群结构;Spearman相关性分析和可解释机器学习(SHapley Additive exPlanations, SHAP)识别关键菌群与代谢表型的关联。
结果
2
Rb1显著降低NASH小鼠血清TC、TG、ALT、AST及LDL-C水平(
P
<
0.05),减少肝脏脂滴积累和纤维化,抑制TNF-α和IL-1β表达,提升闭锁小带蛋白-1(zonula occludens-1, ZO-1)和闭合蛋白(Occludin)水平(
P
<
0.05);增加乳杆菌属、双歧杆菌属等有益菌丰度,减少脱硫弧菌属等有害菌;肠道菌群多样性显著提高(
P
<
0.05)。相关性分析显示,Rb1富集的有益菌属与代谢改善指标呈显著正相关(
P
<
0.05),与炎症及肝损伤标志物呈强负相关(
P
<
0.05)。机器学习模型中ALT为NASH预测的最核心驱动因子。
结论
2
Rb1可通过调节肠道菌群结构、修复肠屏障功能,抑制炎症反应,改善脂质代谢,显著缓解NASH的病理进展。
Objective
2
To investigate the therapeutic effects of ginsenoside Rb1 on non-alcoholic steatohepatitis (NASH) and its mechanisms through modulating gut microbiota and repairing intestinal barriers in liver inflammation and metabolic disorders.
Methods
2
A model NASH mouse was established by high-fat
high-cholesterol diet (HFHCD) feeding. After modeling
the NASH mice were treated with Rb1
via
intraperitoneal injection. An
in vitro
NASH model was induced with oleic acid+cholesterol in HepG2 cells. Serum biochemistry
histopathological observation (HE
Oil Red O
Masson
Sirius Red staining)
and Western blotting (inflammatory and tight junction proteins) were performed. Gut microbiota was analyzed with 16S rRNA gene sequencing. The correlations between key microbiota and metabolic phenotypes were analyzed using Spearman correlation analysis and SHapley Additive exPlanations (SHAP) analysis.
Results
2
Rb1 significantly reduced serum levels of total cholesterol (TC)
triglyceride (TG)
alanine transaminase (ALT)
aspartate aminotransferase (AST) and low-density lipid-cholesterol (LDL-C) in the NASH mice (
P
<
0.05)
decreased lipid accumulation and fibrosis in liver tissues
inhibited TNF-α and IL-1β expression
and increased zonula occludens-1(ZO-1) and Occludin levels (
P
<
0.05). It also boosted beneficial bacteria like
Lactobacillus
and
Bifidobacterium
reduced harmful bacteria such as
Desulfovibrio
and enhanced gut microbiota diversity (
P
<
0.05). Correlation analysis showed that beneficial bacteria enriched by Rb1 were positively correlated with the improvements of metabolic indicators and negatively with inflammatory factors and liver injury markers (
P
<
0.05). The machine learning model identified ALT as the key predictor for NASH.
Conclusion
2
Rb1 can inhibit inflammatory response and improve lipid metabolism by modulating gut microbiota and repairing the intestinal barrier
and thus significantly alleviate NASH progression.
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