目的 探讨山仙颗粒通过调控肠道菌群组成及抑制炎症因子延缓肝癌前病变的机制。方法 将 80 只 SD 大鼠随机分为正常组、模型组及山仙颗粒低、高剂量组。腹腔注射二乙基亚硝胺（DEN）制备肝癌前病变大鼠模 型，造模第二日起灌胃给药，每日 1 次，连续 16 周。血液生化分析肝功能指标；HE 染色观察肝、肠组织形 态学改变；16S rRNA 高通量测序技术检测肠道菌群变化；免疫组化检测增殖细胞相关抗原；Western Blot 法检 测炎症相关蛋白表达情况。结果 与正常组比较，模型组大鼠肝功能相关酶指标含量增高（P＜0.05）；肝组织 病理学改变明显；肝细胞 Ki67 表达增强（P＜0.05）；有益菌厚壁菌门、乳酸杆菌减少（P＜0.05），致病菌变形 杆菌、拟杆菌门增多（P＜0.05）；小肠黏膜进行性损伤；炎症相关蛋白表达升高。与模型组比较，山仙颗粒低、 高剂量组肝功能相关酶指标含量降低（P＜0.05，P＜0.01）；肝脏病理损伤改善；肝细胞 Ki67 表达降低（P＜ 0.05，P＜0.01）；有益菌增多（P＜0.05），致病菌减少（P＜0.05）；小肠黏膜损伤恢复；炎症相关蛋白表达降低 （P＜0.05）。结论 山仙颗粒可通过改善肠道菌群失调、修复肠黏膜损伤，降低肝组织中炎症相关蛋白的表达， 改善 DEN 诱导的大鼠肝癌前病变。

Objective To investigate the mechanism by which Shanxian Granules delay the progression of hepatic precancerous lesions via regulating gut microbiota composition and suppressing inflammatory factors. Methods Eighty SD rats were randomly divided into a normal group， a model group， and low- and high-dose Shanxian Granules groups. A rat model of hepatic precancerous lesions was established by intraperitoneal injection of diethylnitrosamine （DEN）. Intragastric administration began on the second day of modeling，once daily for 16 consecutive weeks. Blood biochemical analysis was performed to assess liver function indices. Morphological changes in liver and intestinal tissues were observed by HE staining. Changes in gut microbiota were detected using 16S rRNA high-throughput sequencing. Immunohistochemistry was used to detect the proliferation cell-related antigen Ki67. Western Blot was employed to measure the expression of inflammation-related proteins. Results Compared with the normal group，the model group showed increased levels of liver function-related enzymes （P＜0.05），significant histopathological changes in the liver， enhanced expression of Ki67 in hepatocytes （P＜0.05），a decrease in beneficial bacteria （Firmicutes，Lactobacillus）（P＜0.05），an increase in pathogenic bacteria （Proteobacteria，Bacteroidetes）（P＜0.05），progressive damage to the small intestinal mucosa， and elevated expression of inflammation-related proteins. Compared with the model group， the low- and high-dose Shanxian Granules groups exhibited decreased levels of liver function-related enzymes （P＜ 0.05， P＜0.01）， improved liver pathological damage， reduced expression of Ki67 in hepatocytes （P＜0.05， P＜ 0.01），an increase in beneficial bacteria （P＜0.05），a decrease in pathogenic bacteria （P＜0.05），recovery of small intestinal mucosal damage， and decreased expression of inflammation-related proteins （P＜0.05）. Conclusion Shanxian Granules can ameliorate DEN-induced hepatic precancerous lesions in rats by improving gut microbiota dysbiosis，repairing intestinal mucosal damage，and reducing the expression of inflammation-related proteins in liver tissue.

R285.5

国家自然科学基金项目（81703842）；陕西省重点研发计划项目（2024SF-YBXM-147）；秦创原中医药产业创新聚集区项目（L2024- QCY-ZYYJJQ- X217）；陕西中医药大学研究生创新实践能力提升项目（CXSJ202503）；咸阳市重点研发计划项目（L2025-ZDYF-JBFZ-017）。