5-羟色胺及其受体在肝泡型棘球蚴病中的表达特征和临床意义

Expression and clinical significance of 5-HT and its receptor in hepatic alveolar echinococcosis

摘要

目的：探讨5-羟色胺（5-HT）及其受体（5-HTR2B）在肝泡型棘球蚴病（HAE）中的表达特征，分析其与肝脏损伤及纤维化的相关性，并评估其作为临床病情评估工具的潜在价值。方法：纳入肝血管瘤（HEM）15例、肝癌（HCC）15例及HAE 15例。所有受试者均采集术前空腹静脉血，并在手术切除病灶时获取病灶周围的肝组织。采用ELISA法比较3组间血清5-HT、白细胞介素33（IL-33）水平的差异，利用定量qPCR、Western blot及免疫组织化学方法分析肝组织中5-HTR2A/2B及纤维化标志物α-平滑肌肌动蛋白（α-SMA）、I型胶原蛋白（COL-1）的相关性。结果：HAE组的血清5-HT和IL-33水平显著高于HCC和HEM组（P<0.05），且HAE组中两者呈正相关（P<0.05）。在HAE组中，5-HTR2B与IL-33（P<0.05）及纤维化标志物（α-SMA、COL-1）高度相关（P<0.05），且定位于纤维隔内。结论：IL-33可能通过诱导5-HT分泌，进而促进肝纤维化进程。血清IL-33与5-HT联合检测有望作为评估HAE肝纤维化的无创标志物，然而其具体机制仍需进一步研究验证。

Abstract

Objective: To investigate the expression patterns of serotonin (5-HT) and its receptor (5-HTR2B) in hepatic alveolar echinococcosis (HAE), analyze their correlation with liver injury and fibrosis, and evaluate their potential value as clinical assessment tools. Methods: This study enrolled 45 patients admitted to the Center of Digestive and Vascular Surgery, First Affiliated Hospital of Xinjiang Medical University between 2023 and 2024, comprising 15 cases of hepatic hemangioma (HEM), 15 cases of hepatocellular carcinoma (HCC), and 15 cases of HAE. Preoperative fasting venous blood samples were collected from all subjects, and liver tissues adjacent to the lesions were obtained during surgical resection. Serum levels of 5-HT and interleukin-33 were compared among the three groups using ELISA. The expression of 5-HT receptors (5-HTR2A/2B) and fibrosis markers (Alpha-smooth muscle actin，α-SMA; Collagen type I，COL-1) in liver tissues was analyzed using qPCR, Western blot (WB), and immunohistochemistry (IHC), and their correlations were examined. Results: Serum levels of 5-HT and IL-33 in the HAE group were significantly higher than those in the HCC and HEM groups (P<0.05), and a positive correlation was observed between them (P<0.05). In liver tissue, the expression of 5-HTR2B showed a strong positive correlation with IL-33 (P<0.05) and with fibrosis markers (α-SMA and COL-1; P<0.05), and was localized within the fibrotic septa. Conclusion: IL-33 may promote the progression of liver fibrosis by inducing 5-HT secretion. The combined detection of serum IL-33 and 5-HT holds promise as a non-invasive biomarker for assessing liver fibrosis in HAE; however, the precise underlying mechanisms require further investigation and validation.

关键词

肝泡型棘球蚴病 / 5-HT / 5-HTR2B / IL-33/ST2信号轴 / 肝纤维化

Key words

Alveolar echinococcosis / 5-HT / 5-HTR2B / IL-33/ST2 axis / Liver fibrosis

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基金资助

国家自然科学基金(82260411)

国家自然科学基金(82270632)

新疆维吾尔自治区天山英才培养计划青年拔尖人才项目(2024TSYCCXO105)

新疆医科大学国家级高层次人才培育项目(XYD2024GR08)