目的 从荔枝核总黄酮（total flavonoids from Litchi Semen，TFL）调节肠道微环境的角度探讨其抗肝纤维化（hepatic fibrosis，HF）的作用机制。方法 采用40%四氯化碳（carbon tetrachloride，CCl₄）-花生油溶液背部sc构建HF大鼠模型，将HF大鼠分为模型组、扶正化瘀组（450 mg/kg）及TFL低、中、高剂量（45、90、180 mg/kg）组，连续ig给药8周后，Masson染色观察各组大鼠肝脏组织病理变化；ELISA法检测大鼠血清HF标志物IV型胶原（collagen type IV，Col-IV）、透明质酸（hyaluronic acid，HA）、III型前胶原（procollagen type III，PC III）、层黏连蛋白（laminin，LN）的含量；检测血清中丙氨酸氨基转移酶（alanine aminotransferase，ALT）、天冬氨酸氨基转移酶（aspartate aminotransferase，AST）含量评价大鼠肝功能，鲎试剂检测血清内毒素水平；16S rRNA高通量测序分析肠道菌群结构；采用Western blotting法检测大鼠回肠组织闭锁小带蛋白-1（zonula occludens-1，ZO-1）、闭合蛋白（occludin）、封闭蛋白2（claudin 2）的表达。结果TFL各给药组均能不同程度的改善HF大鼠肝脏胶原沉积情况，显著降低血清中Col-IV、PC III、HA、LN、ALT、AST含量（P＜0.01）；显著增加回肠组织ZO-1、occludin蛋白表达（P＜0.05）。TFL能改善HF大鼠肠道菌群多样性，在门、属水平上恢复肠道菌群的正常组成，并同时显著降低入血内毒素水平（P＜0.01）。结论TFL可缓解CCl₄诱导的HF大鼠症状，其机制可能为恢复肠道菌群多样性，改善肠黏膜屏障，从而减少肠源性内毒素入血，进而抑制HF的进展。

Objective The anti-hepatic fibrosis (HF) mechanism of total flavonoids from Litchi Semen (TFL) was investigated from the regulating of intestinal microenvironment. Methods Rats were injected subcutaneously with 40% carbon tetrachloride (CCl₄)-peanut oil solution to induce HF. Then HF rats were divided into model group, Fuzheng Huayu group (450 mg/kg), and TFL low-, medium-, and high-dose (45, 90, and 180 mg/kg) groups. After eight weeks of ig administration, masson staining was performed to observe the histopathological changes in the liver of rats, ELISA was performed to detect the content of serum hepatic fibrosis markers, collagen type Ⅳ (Col-IV), hyaluronic acid (HA), procollagen type III (PC III), and laminin (LN); alanine aminotransferase (ALT); aspartate aminotransferase (AST) were measured to evaluate the rat hepatic function, horseshoe crab reagent was used to detect serum endotoxin levels. 16S rRNA high-throughput sequencing was used to analyze the structure of the intestinal flora. Western blotting was used to detect zonula occludens-1 (ZO-1), occludin, and claudin 2 in ileum tissue. Results All dose of TFL treatment decrease the hepatic collagen deposition in HF rats, and significantly reduced the serum levels of Col-IV, PC III, HA, LN, ALT and AST (P < 0.01); meanwhile, it significantly increased ileal ZO-1, Occludin proteins (P < 0.05). Moreover, TFL treatment improved the intestinal flora diversity in hepatic fibrosis rats, restored the composition of intestinal flora at the portal and generic levels, and significantly reduced the level of blood-entered endotoxin (P < 0.01). Conclusion TFL could attenuate CCl₄-induced HF rats, and the mechanism may lie in restoring the diversity of intestinal flora and improving the intestinal mucosal barrier, thus alleviating the chronic exposure to gut-derived endotoxins, ultimately inhibiting the progression of hepatic fibrosis.

R285.5

国家自然科学基金项目(82160834);广西壮瑶药重点实验室开放课题(GXZYZZ2022-15);广西中医药大学桂派杏林拔尖人才项目(2022C007);广西中医药大学岐黄工程高层次人才团队培育项目(202405);中药学广西一流学科[桂教科研(2022)1号];广西