丁二磺酸腺苷蛋氨酸对酒精性肝病患者JAK2/STAT3通路及肝纤维化的影响

Effect of ademetionine on JAK2/STAT3 pathway and liver fibrosis in patients with alcoholic liver disease

摘要

目的 观察丁二磺酸腺苷蛋氨酸（SAMe）对酒精性肝病（ALD）患者Janus激酶2/信号转导及转录激活因子3（JAK2/STAT3）通路及肝纤维化的影响。方法 前瞻性选取南阳市第一人民医院2023年9月—2024年9月收治的96例ALD患者为研究对象,设计随机对照试验。通过简单随机数字表法将其分为常规组和试验组,每组48例。常规组实施常规药物治疗,试验组采用SAMe联合常规药物治疗,比较2组患者治疗开始前1天、治疗结束后第1天的JAK2/STAT3蛋白表达水平、炎症指标、氧化应激指标、肝纤维化指标。治疗后随访1年,比较2组患者的肝功能恢复情况。分析JAK2/STAT3通路蛋白与临床指标的相关性。结果 治疗后,试验组的JAK2、STAT3表达水平均低于常规组（P<0.05）。试验组的白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、活性氧（ROS）表达水平均低于常规组,谷胱甘肽（GSH）表达水平高于常规组（P<0.05）。试验组的Ⅲ型前胶原氨基端肽（PⅢNP）、Ⅳ型胶原（C-Ⅳ）、透明质酸（HA）、层黏连蛋白（LN）表达水平均低于常规组（P<0.05）。截至随访结束时,试验组的谷丙转氨酶（ALT）、谷草转氨酶（AST）、总胆红素（TBil）表达水平均低于常规组（P<0.05）。JAK2、STAT3分别与IL-6、IL-1β、ROS、PⅢNP、C-Ⅳ、HA、LN呈正相关,与GSH呈负相关（P<0.05）。结论 SAMe可减轻ALD患者的炎症反应及氧化应激损伤,对延缓肝纤维化进程及促进肝功能恢复均有积极影响,其作用机制可能与抑制JAK2/STAT3通路密切相关。

Abstract

Objective To investigate the effect of S-adenosylmethionine (SAMe) on Janus kinase 2/ signal transducer and activator of transcription 3 (JAK2/STAT3) pathway and liver fibrosis in patients with alcoholic liver disease (ALD). Methods A total of 96 ALD patients admitted to Nanyang First People's Hospital from September 2023 to September 2024 were prospectively selected as the research objects, and a randomized controlled trial was designed. They were divided into the routine group and the experimental group by the simple random number table method, with 48 cases in each group. The conventional group was treated with conventional drug therapy, and the experimental group was treated with SAMe combined with conventional drug therapy. The expression levels of JAK2/STAT3 protein, inflammatory indicators, oxidative stress indicators, and liver fibrosis indicators of the two groups were compared 1 day before and 1 day after treatment. The patients were followed up for one year after treatment, and the recovery of liver function was compared between the two groups. The correlation between JAK2/STAT3 pathway proteins and clinical indicators was analyzed. Results After treatment, the expression levels of JAK2 and STAT3 in the experimental group were lower than those in the conventional group (P<0.05). The expression levels of interleukin-6 (IL-6), interleukin-1β (IL-1β) and reactive oxygen species (ROS) in the experimental group were lower than those in the conventional group, and the expression level of glutathione (GSH) was higher than that in the conventional group (P<0.05). The experimental group had significantly lower expression levels of procollagen type Ⅲ amino terminal peptide (PⅢNP), collagen type Ⅳ (C-Ⅳ), hyaluronic acid (HA), and laminin (LN) than the conventional group (P<0.05). At the end of follow-up, the expression levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil) in the experimental group were lower than those in the conventional group (P<0.05). JAK2 and STAT3 were positively correlated with IL-6, IL-1β, ROS, PⅢNP, C-Ⅳ, HA, LN, respectively, and negatively correlated with GSH (P<0.05). Conclusion SAMe can reduce inflammatory response and oxidative stress injury in patients with ALD, and has a positive effect on delaying the process of liver fibrosis and promoting the recovery of liver function. Its mechanism may be closely related to the inhibition of JAK2/STAT3 pathway.

关键词

酒精性肝病 / 丁二磺酸腺苷蛋氨酸 / Janus激酶2/信号转导及转录激活因子 / 肝纤维化

Key words

alcoholic liver disease / adenosylmethionine succinate / JAK2/STAT3 / liver fibrosis

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基金资助

河南省医学科技攻关项目（LHGJ20201432）