[1]高小贤,谭福雄,张媛媛,等.基于NLRP3/Caspase-1/IL-1β通路研究柔木丹治疗肝纤维化机制[J].陕西中医,2026,(2):171-177.[doi:DOI:10.3969/j.issn.1000-7369.2026.02.005]
　GAO Xiaoxian,TAN Fuxiong,ZHANG Yuanyuan,et al.Mechanism of Roumu Dan in treatment of liver fibrosis studied based on NLRP3/Caspase-1/IL-1β pathway[J].,2026,(2):171-177.[doi:DOI:10.3969/j.issn.1000-7369.2026.02.005]
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基于NLRP3/Caspase-1/IL-1β通路研究柔木丹治疗肝纤维化机制

《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2026年2期
页码:
171-177
栏目:
基础研究
出版日期:
2026-02-05

文章信息/Info

Title:
Mechanism of Roumu Dan in treatment of liver fibrosis studied based on NLRP3/Caspase-1/IL-1β pathway
作者:
高小贤1; 谭福雄2; 张媛媛3; 张杰4; 樊晓丹4; 寇小妮4; 王小锋4
（1.陕西中医药大学，陕西 咸阳 712046；2.西安中医脑病医院，陕西 西安 710018；3.秦皇岛市第二医院，河北 秦皇岛066600；4.陕西中医药大学附属医院，陕西 咸阳712000）
Author(s):
GAO Xiaoxian1; TAN Fuxiong2; ZHANG Yuanyuan3; ZHANG Jie4; FAN Xiaodan4; KOU Xiaoni4; WANG Xiaofeng4
(1.Shaanxi University of Chinese Medicine,Xianyang 712046,China；2.Xi’an TCM Hospital of Encephalopathy,Xi’an 710018，China;3.The Second Hospital of Qinhuangdao,Qinhuangdao 066600，China;4.Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000，China)
关键词:
肝纤维化; 柔木丹; NLRP3/Caspase-1/IL-1β通路; 细胞焦亡; 炎症反应; 胶原沉积
Keywords:
Hepatic fibrosis; Roumu Dan; NLRP3/Caspase-1/IL-1β pathway; Cellular pyroptosis; Inflammatory response; Collagen deposition
分类号:
R 289
DOI:
DOI:10.3969/j.issn.1000-7369.2026.02.005
文献标志码:
A
摘要:
目的：基于NLRP3/Caspase-1/IL-1β通路探讨柔木丹改善肝纤维化（HF）作用和机制，为柔木丹治疗HF提供理论依据和实验支持。方法：60只SPF级雄性SD大鼠，随机分为空白组、模型组、柔木丹低剂量组、柔木丹中剂量组、柔木丹高剂量组和扶正化瘀组（n=10）。采用四氯化碳（CCl4）混悬溶液诱导大鼠HF模型，给予柔木丹、扶正化瘀胶囊灌胃治疗。通过血清测定转氨酶活性；苏木精-伊红染色、Masson染色观察病理变化；酶联免疫吸附法检测白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、金属蛋白酶组织抑制因子-1（TIMP-1）、基质金属蛋白酶-2（MMP-2）水平。免疫组织化学法检测α-平滑肌肌动蛋白（α-SMA）、Ⅰ型胶原（Collagen Ⅰ）蛋白表达；蛋白质印迹实验检测核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）、半胱天冬氨酸蛋白酶-1（Caspase-1）、IL-1β、Gasdermin D（GSDMD）、转化生长因子-β1（TGF-β1）的表达。逆转录实时荧光定量聚合酶链反应法检测肝组织NLRP3、Caspase-1及IL-1β mRNA的转录水平。结果：与空白组相比，模型组大鼠HF程度显著加重。与模型组相比，柔木丹各剂量组和扶正化瘀组大鼠的丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）活性降低；IL-1β、TNF-α、TIMP-1、MMP-2的表达水平降低；NLRP3、Caspase-1、IL-1β、GSDMD、TGF-β1蛋白表达水平降低；NLRP3、Caspase-1及IL-1β mRNA的转录水平降低，且柔木丹改善效果呈剂量依赖性，差异有统计学意义（均P＜0.05）。结论：柔木丹可有效改善CCl4诱导的大鼠HF。其机制可能与抑制NLRP3/Caspase-1/IL-1β通路活化、减少炎症因子释放、抑制肝星状细胞活化与增殖、减少肝组织胶原沉积有关。
Abstract:
Objective:To explore effect and mechanism of Roumu Dan on improving liver fibrosis (HF) based on the NLRP3/Caspase-1/IL-1β pathway,and to provide theoretical basis and experimental support for the treatment of HF with Roumu Dan.Methods:60 SPF male SD rats were randomly divided into blank group,model group,low-dose Roumu Dan group,medium-dose Roumu Dan group,high-dose Roumu Dan group and Fuzheng Huayu Capsule group (n=10).The HF model was induced by carbon tetrachloride (CCl4) suspension solution,and Roumu Dan and Fuzheng Huayu capsule were administered by gavage.The activities of transaminases in serum were determined.Pathological changes were observed by hematoxylin-eosin staining and Masson staining.The levels of interleukin-1β (IL-1β),tumor necrosis factor-α (TNF-α),tissue inhibitor of metalloproteinase-1 (TIMP-1),and matrix metalloproteinase-2 (MMP-2) were detected by enzyme-linked immunosorbent assay.The protein expressions of α-smooth muscle actin (α-SMA) and type I collagen (Collagen I) were detected by immunohistochemistry.The expressions of NLRP3,Caspase-1,IL-1β,Gasdermin D (GSDMD),and transforming growth factor-β1 (TGF-β1) were detected by Western blot.The transcriptional levels of NLRP3,Caspase-1 and IL-1β mRNA in liver tissue were detected by reverse transcription real-time fluorescence quantitative polymerase chain reaction.Results:Compared with the blank group,the degree of HF in the model group were significantly aggravated.Compared with the model group,the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the rats of each dose group of Roumu Dan and the Fuzheng Huayu capsule group were decreased.The expression levels of IL-1β,TNF-α,TIMP-1 and MMP-2 were decreased.The protein expression levels of NLRP3,Caspase-1,IL-1β,GSDMD and TGF-β1 were decreased.The transcriptional levels of NLRP3,Caspase-1 and IL-1β mRNA were decreased,and the improvement effect of Roumu Dan was dose-dependent,statistically significant differences (all P＜0.05).Conclusion:Roumu Dan can effectively improve CCl4-induced HF in rats.The mechanism may be related to the inhibition of NLRP3/Caspase-1/IL-1β pathway activation,reduction of inflammatory factor release,inhibition of hepatic stellate cell activation and proliferation,and reduction of collagen deposition in liver tissue.

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备注/Memo

备注/Memo:
国家自然科学基金资助项目（81704073）；陕西省科技厅重点研发计划项目（2022SF-302）；陕西中医药大学附属医院国科金培育项目（2020MS011）；陕西中医药大学校级科研资助项目（2020XG03）
更新日期/Last Update: 2026-02-09