Tao Yujing, Niu Qun, Yao Yuanqian, Wang Kaixin, Dong Haijian, Zhao Xin, Zeng Zijian, Li Hui
Hospital of Chengdu University of Traditional Chinese Medicine, TCM Hospital of Sichuan Province, Chengdu, Sichuan, China.
School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
Front Pharmacol. 2025 Jan 7;15:1528100. doi: 10.3389/fphar.2024.1528100. eCollection 2024.
Liver fibrosis is a globally prevalent chronic liver disease, often representing the advanced stage of various chronic liver conditions. Despite its widespread occurrence, there is currently no widely accepted or effective treatment for liver fibrosis. However, increasing evidence supports the efficacy of Traditional Chinese Medicine (TCM) in inhibiting the progression of fibrosis. In this study, we explored the effects and potential mechanisms of Qizhu-Ruogan-Granules (QZRG), a formulation from the Affiliated Hospital of the Chengdu University of TCM, on carbon tetrachloride (CCl4)-induced liver fibrosis in mice.
A total of 40 male C57BL/6J mice were randomly divided into five groups (n = 8 per group), with liver fibrosis induced by injecting 10% CCl for 15 weeks. From the 7th week onward, QZRG granules were administered orally to the treatment groups at low, medium, and high doses. To assess liver function, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were measured. Liver morphology and fibrosis were evaluated using hematoxylin-eosin (H&E) and Masson's trichrome staining, while gene and protein expression levels were analyzed through quantitative reverse transcription polymerase chain reaction (RT-PCR) and western blot techniques.
The results showed that QZRG granules significantly reduced serum levels of AST, ALT, and ALP in CCl-treated mice, alleviated liver damage, and reduced collagen accumulation. Furthermore, QZRG granules inhibited the expression of apoptosis-related proteins BAX, Caspase9, Caspase8, and Caspase3, while reducing P2Y14 expression in fibrotic liver tissues. Additionally, QZRG granules suppressed the proliferation of activated hepatic stellate cells.
Our findings suggest that QZRG granules may exert anti-fibrotic effects by downregulating P2Y14 expression and effectively slowing the progression of liver fibrosis.
肝纤维化是一种全球普遍存在的慢性肝病，通常代表各种慢性肝脏疾病的晚期阶段。尽管其广泛发生，但目前尚无广泛接受或有效的肝纤维化治疗方法。然而，越来越多的证据支持中医在抑制纤维化进展方面的疗效。在本研究中，我们探讨了成都中医药大学附属医院的制剂芪术柔肝颗粒（QZRG）对四氯化碳（CCl4）诱导的小鼠肝纤维化的影响及潜在机制。
将40只雄性C57BL/6J小鼠随机分为五组（每组n = 8），通过注射10% CCl4持续15周诱导肝纤维化。从第7周起，低、中、高剂量的QZRG颗粒口服给药至各治疗组。为评估肝功能，测量血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和碱性磷酸酶（ALP）水平。使用苏木精-伊红（H&E）和Masson三色染色评估肝脏形态和纤维化，同时通过定量逆转录聚合酶链反应（RT-PCR）和蛋白质印迹技术分析基因和蛋白质表达水平。
结果显示，QZRG颗粒显著降低了CCl4处理小鼠的血清AST、ALT和ALP水平，减轻了肝脏损伤，并减少了胶原蛋白积累。此外，QZRG颗粒抑制了凋亡相关蛋白BAX、Caspase9、Caspase8和Caspase3的表达，同时降低了纤维化肝组织中P2Y14的表达。此外，QZRG颗粒抑制了活化肝星状细胞的增殖。
我们的研究结果表明，QZRG颗粒可能通过下调P2Y14表达发挥抗纤维化作用，并有效减缓肝纤维化的进展。
