目的 從荔枝核總黃酮（total flavonoids from Litchi Semen，TFL）調(diào)節(jié)腸道微環(huán)境的角度探討其抗肝纖維化（hepatic fibrosis，HF）的作用機制。方法 采用40%四氯化碳（carbon tetrachloride，CCl₄）-花生油溶液背部sc構(gòu)建HF大鼠模型，將HF大鼠分為模型組、扶正化瘀組（450 mg/kg）及TFL低、中、高劑量（45、90、180 mg/kg）組，連續(xù)ig給藥8周后，Masson染色觀察各組大鼠肝臟組織病理變化；ELISA法檢測大鼠血清HF標(biāo)志物IV型膠原（collagen type IV，Col-IV）、透明質(zhì)酸（hyaluronic acid，HA）、III型前膠原（procollagen type III，PC III）、層黏連蛋白（laminin，LN）的含量；檢測血清中丙氨酸氨基轉(zhuǎn)移酶（alanine aminotransferase，ALT）、天冬氨酸氨基轉(zhuǎn)移酶（aspartate aminotransferase，AST）含量評價大鼠肝功能，鱟試劑檢測血清內(nèi)毒素水平；16S rRNA高通量測序分析腸道菌群結(jié)構(gòu)；采用Western blotting法檢測大鼠回腸組織閉鎖小帶蛋白-1（zonula occludens-1，ZO-1）、閉合蛋白（occludin）、封閉蛋白2（claudin 2）的表達。結(jié)果TFL各給藥組均能不同程度的改善HF大鼠肝臟膠原沉積情況，顯著降低血清中Col-IV、PC III、HA、LN、ALT、AST含量（P＜0.01）；顯著增加回腸組織ZO-1、occludin蛋白表達（P＜0.05）。TFL能改善HF大鼠腸道菌群多樣性，在門、屬水平上恢復(fù)腸道菌群的正常組成，并同時顯著降低入血內(nèi)毒素水平（P＜0.01）。結(jié)論TFL可緩解CCl₄誘導(dǎo)的HF大鼠癥狀，其機制可能為恢復(fù)腸道菌群多樣性，改善腸黏膜屏障，從而減少腸源性內(nèi)毒素入血，進而抑制HF的進展。

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

國家自然科學(xué)基金項目(82160834);廣西壯瑤藥重點實驗室開放課題(GXZYZZ2022-15);廣西中醫(yī)藥大學(xué)桂派杏林拔尖人才項目(2022C007);廣西中醫(yī)藥大學(xué)岐黃工程高層次人才團隊培育項目(202405);中藥學(xué)廣西一流學(xué)科[桂教科研(2022)1號];廣西