恩替卡韦对慢性乙型肝炎肝纤维化患者IL-6/STAT3/SOCS3通路的影响

IF 0.6 4区医学 Q4 PHARMACOLOGY & PHARMACY

Tropical Journal of Pharmaceutical Research Pub Date : 2023-10-08 DOI:10.4314/tjpr.v22i9.22

Shuqiao Wang, Ziqi Sui, Kaili Peng, Hefei Cheng

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引用次数: 0

摘要

目的:评价恩替卡韦(ENT)对慢性乙型肝炎(CHB)肝纤维化患者的影响及其与白细胞介素(IL)-6/转录信号传导激活因子3 (STAT3)/细胞因子信号传导抑制因子3 (SOCS3)通路的关系。方法:31例肝纤维化患者给予耳鼻喉科治疗，剂量为0.5 mg/d，连续48周。采用酶联免疫吸附试验(ELISA)检测治疗前后患者血清相关蛋白水平。体外培养人肝星状细胞(hsc)，并将其分为对照组、转化生长因子β1 (TGF-β1)诱导组(TGF-β1组)和耳鼻炎治疗组(TGF-β1 +耳鼻炎组)。ELISA法检测上清蛋白水平，qRT-PCR法检测相关基因表达水平。免疫荧光法观察α-SMA的表达，Western blotting检测相关蛋白水平。结果:耳鼻喉科治疗显著降低(p <0.01) IL-6、STAT3表达升高，SOCS3表达显著降低(p <0.01)肝纤维化患者透明质酸(HA)、IV型胶原(IVC)、层粘连蛋白(LN)和III型前胶原(PCIII)的浓度。TGF-β1显著(p <0.01) IL-6、STAT3和col -1表达升高，组织金属蛋白酶抑制剂-1 (TIMP-1)抑制人造血干细胞中SOCS3的表达并诱导纤维化。恩替卡韦减轻TGF-β1诱导的hsc纤维化(p <0.01)。结论:恩替卡韦通过调节IL- 6/STAT3/SOCS3通路对慢性乙型肝炎肝纤维化有积极作用。未来的研究将集中于进行更大规模的临床试验，以进一步验证这些发现，并探索耳鼻喉科对肝纤维化进展和患者预后的长期影响。

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Effect of entecavir on IL-6/STAT3/SOCS3 pathway in patients with chronic hepatitis B-induced liver fibrosis

Purpose: To evaluate the impact of entecavir (ENT) on patients with liver fibrosis resulting from chronic hepatitis B (CHB) and its association with the interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3)/suppressor of cytokine signaling 3 (SOCS3) pathway.Methods: Thirty-one patients with liver fibrosis received ENT at a dose of 0.5 mg/day for 48 weeks. Relevant protein levels in patient’s serum before and after treatment were assayed using enzyme-linked immunosorbent assay (ELISA). Furthermore, human hepatic stellate cells (HSCs) were cultured in vitro and divided into three groups: control, transforming growth factor beta 1 (TGF-β1) induction (TGF-β1 group), and ENT treatment (TGF-β1 + ENT group). Protein levels in the supernatant were assayed using ELISA, while the expression levels of related genes were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Expression of α-SMA was visualized using immunofluorescence assay and the relevant protein levels were determined by Western blotting.Results: Treatment with ENT significantly decreased (p < 0.01) IL-6 and STAT3 expression, increased SOCS3 expression and significantly reduced (p < 0.01) the concentrations of hyaluronic acid (HA), type IV collagen (IVC), laminin (LN) and pro-collagen type III (PCIII) in patients with liver fibrosis. TGF-β1 significantly (p < 0.01) elevated IL-6, STAT3 and Col-I expressions and a tissue inhibitor of metalloproteinases-1 (TIMP-1) suppressed the expression of SOCS3 in human HSCs and induced fibrosis. Entecavir mitigated TGF-β1-induced fibrogenesis in HSCs (p < 0.01).Conclusion: Entecavir has a positive effect on liver fibrosis resulting from CHB by regulating IL- 6/STAT3/SOCS3 pathway. Future research will focus on conducting larger clinical trials to further validate these findings and explore the long-term effects of ENT on liver fibrosis progression and patient outcomes.

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来源期刊

Tropical Journal of Pharmaceutical Research 医学-药学

CiteScore

1.00

自引率

33.30%

发文量

490

审稿时长

4-8 weeks

期刊介绍： We seek to encourage pharmaceutical and allied research of tropical and international relevance and to foster multidisciplinary research and collaboration among scientists, the pharmaceutical industry and the healthcare professionals. We publish articles in pharmaceutical sciences and related disciplines (including biotechnology, cell and molecular biology, drug utilization including adverse drug events, medical and other life sciences, and related engineering fields). Although primarily devoted to original research papers, we welcome reviews on current topics of special interest and relevance.