Li Lixiang, Niu Xiaoyong, Zhang Wanzong, Wang Ziyu, Zhang Shengming, Zhang Qi, Qi Wei, Jing Wenshan, Hu Gaobin, Huang Long, Li Ziyi, Feng Qiyu, Peng Hui, Yu Qingsheng
Department of General Surgery, The First Affiliated Hospital of Anhui University of Chinese Medicine Hefei 230031, Anhui, P. R. China.
Department of General Surgery, The People's Hospital of Lujiang County No. 32, Wenming Middle Road, Lujiang County, Hefei 230036, Anhui, P. R. China.
Am J Transl Res. 2024 Nov 25;16(11):7186-7199. doi: 10.62347/VXHU6738. eCollection 2024.
Hepatolithiasis (HL) is a complex liver and biliary disorder characterized by high rates of recurrence. This study aimed to evaluate the efficacy of Twelve Shugan Lidan Granules (TSLG), a compound herbal traditional Chinese formulation, in the treatment of HL, as well as to investigate its underlying mechanism.
A retrospective analysis was conducted involving 157 patients diagnosed with HL, who were divided into two groups: the control group and the research group. In the control group, no treatment was given postoperatively, while in the research group, TSLG was orally administered three times a day postoperatively for two months. Both groups were followed up by telephone at 1 month, 2 months, and 3 months postoperatively. Liver function indicators were measured before and after surgery, and miRNA expression profiling was analyzed using high-throughput sequencing (HTS). Additionally, the expression levels of related proteins were assessed through western blots.
Postoperative liver function indicators were significantly lower in the research group compared to the control group (P < 0.05). Additionally, 64 miRNAs were differentially expressed in HL patients. Further analysis of 64 miRNAs revealed their abnormal targeting of the Hippo signaling pathway. Further experimental results indicate that TAZ protein expression is elevated in HL patients, reflecting abnormal activation of the Hippo signaling pathway in these patients. TSLG treatment significantly reduced the expression of YAP, TAZ, and SREBP-2 proteins, while increasing the expression of p-YAP and p-TAZ proteins (all P < 0.05). Furthermore, TSLG inhibited the Extracellular Acidification Rate (ECAR) in LPS-induced WRL68 cells.
TSLG effectively improved postoperative liver function by downregulating sterol regulatory element-binding protein-2 (SREBP-2) and inhibiting the Hippo signaling pathway.
肝内胆管结石（HL）是一种复杂的肝胆疾病，其复发率很高。本研究旨在评估复方中药制剂十二疏肝利胆颗粒（TSLG）治疗HL的疗效，并探讨其潜在机制。
对157例诊断为HL的患者进行回顾性分析，将其分为两组：对照组和研究组。对照组术后不给予治疗，而研究组术后每天口服TSLG三次，持续两个月。两组在术后1个月、2个月和3个月通过电话进行随访。在手术前后测量肝功能指标，并使用高通量测序（HTS）分析miRNA表达谱。此外，通过蛋白质印迹法评估相关蛋白的表达水平。
研究组术后肝功能指标显著低于对照组（P < 0.05）。此外，HL患者中有64种miRNA差异表达。对64种miRNA的进一步分析揭示了它们对Hippo信号通路的异常靶向。进一步的实验结果表明，HL患者中TAZ蛋白表达升高，反映了这些患者中Hippo信号通路的异常激活。TSLG治疗显著降低了YAP、TAZ和SREBP-2蛋白的表达，同时增加了p-YAP和p-TAZ蛋白的表达（均P < 0.05）。此外，TSLG抑制了脂多糖诱导的WRL68细胞中的细胞外酸化率（ECAR）。
TSLG通过下调固醇调节元件结合蛋白-2（SREBP-2）并抑制Hippo信号通路，有效改善了术后肝功能。
