探究利胆消石合剂预防内镜下逆行性胰胆管造影术术后胆总管结石复发的作用机制  

Exploring the Mechanism of Lidan Xiaoshi Mixture(利胆消石合剂)in Preventing the Recurrence of CBDS After ERCP

作　　者：卞昊宇 吕福琪 魏骄阳 姚玉璞[1] 胡蝶羽 于雪[2] 王惠临 张立平[1] BIAN Haoyu;LYU Fuqi;WEI Jiaoyang;YAO Yupu;HU Dieyu;YU Xue;WANG Huilin;ZHANG Liping(Dongfang Hospital of Beijing University of Chinese Medicine,Beijing 100078,China;Beijing University of Chinese Medicine,Beijing 100029,China;Jincheng People's Hospital,Jincheng 048026,Shanxi,China)

机构地区：[1]北京中医药大学东方医院,北京100078 [2]北京中医药大学,北京100029 [3]晋城市人民医院,山西晋城048026

出　　处：《辽宁中医药大学学报》2025年第5期9-16,共8页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：北京中医药大学基本科研业务费项目(2023-JYB-JBZD-004)。

摘　　要：目的探究利胆消石合剂是否能通过改善肝脏组织中核因子-κB(NF-κB)介导的法尼醇X受体(FXR)/胆盐输出泵(BSEP)、多药耐药相关蛋白2(MRP2)信号通路,增强胆汁排泄的动力;上调肝脏组织内合成胆汁酸的关键限速酶细胞色素p450家族7亚家族A成员1(CYP7A1),恢复肝脏正常合成胆汁酸的功能,从而预防胆总管结石的复发。方法使用普通级Dunkin Hartley雄性豚鼠共85只。采用胆道插管、注射复发型胆总管结石患者胆道细菌培养液的方式制备胆道结石复发动物模型后,将动物分成模型组、假手术组、胆宁片组、中药低剂量组、中药中剂量组、中药高剂量组,予模型组和假手术组蒸馏水灌胃处理,予胆宁片组胆宁片混悬液灌胃,予中药各剂量组相应浓度的中药灌胃。HE染色法染色后对豚鼠肝脏组织进行组织形态学观察,ELISA法检测豚鼠肝脏组织中脂多糖(LPS)、白细胞介素-1β(IL-1β)、FXR、CYP7A1的含量,Western blot法检测豚鼠肝脏组织中的NF-κB、BSEP、MRP2蛋白的表达情况;液相色谱法检测各组动物模型肝脏组织中胆汁酸的含量,并比较各组差异。结果在炎症指标方面,模型组、胆宁片组、中药各剂量组LPS含量显著高于假手术组;胆宁片组、中药各剂量组LPS含量显著低于模型组;中药各剂量组LPS含量显著高于胆宁片组。假手术组、胆宁片组、中药各剂量组IL-1β含量显著低于模型组;中药各剂量组IL-1β含量显著高于胆宁片组。在NF-κB/FXR、BSEP信号通路方面,胆宁片组、中药各剂量组NF-κB p65蛋白显著低于模型组。模型组、胆宁片组、中药各剂量组FXR含量显著高于假手术组;胆宁片组、中药各剂量组FXR含量显著低于模型组;中药低剂量组、中药高剂量组FXR含量显著高于胆宁片组。中药中剂量组BSEP蛋白含量显著高于模型组;中药中剂量组、中药高剂量组BSEP蛋白含量显著高于假手术组;中药中剂量组BObjective To investigate whether Lidan Xiaoshi Misture(利胆消石合剂,LDXSM)can enhance the dynamics of bile excretion by improving the nuclear factor kappa-B(NF-κB)-mediated FXR/BSEP and MRP2 signalling pathways in liver tissues and prevent recurrence of common bile duct stones(CBDS)by increasing the key rate-limiting enzyme CYP7A1 for the synthesis of bile acids within liver tissues and restoring the liver's function of synthesising bile acids.Methods A total of 85 Dunkin Hartley male guinea pigs were used.The animal model of recurrent bile duct stones was prepared by biliary intubation and injection of biliary bacterial culture medium from patients with recurrent CBDS,and then the animals were divided into the model group,the sham-operated group,the Danning tablets(DNTs)group,the low-dose group of LDXSM,the medium-dose group of LDXSM,the high-dose group of LDXSM.The model group and the sham-operated group were treated with gavage of distilled water,and the DNTs group was gavaged with the DNTs suspension,and the respective dosage groups were gavaged with the corresponding concentration of LDXSM.The histomorphological observation of guinea pig liver tissues was carried out after the application of HE staining method,and the contents of lipopolysaccharide(LPS),interleukin-1 Beta(IL-1β),CYP7A1 and FXR in guinea pig liver tissues were detected by ELISA method,and the expressions of NF-κB,BSEP and MRP2 proteins in guinea pig liver tissues were detected by Western blot method and the content of bile acids in liver tissues of guinea pigs in each group was measured by liquid chromatography method and the differences between groups were then compared.Results In terms of inflammatory biomarkers,the concentration of LPS in the model group,DNTs group,three different-dosed groups of LDXSM was significantly higher than that in the sham-operated group;the concentration of LPS in the DNTs group and three different-dosed groups of LDXSM was significantly lower than that in model group,and the concentration of LPS in thre

关 键 词：利胆消石合剂 复发型胆总管结石 胆汁排泄 胆汁酸谱 

分 类 号：R256.4[医药卫生—中医内科学]