胍丁胺对实验性糖尿病舌下腺功能障碍和胰腺损伤的剂量依赖性保护作用：来自组织学、生化和免疫组织化学分析的证据

摘要(中文译文)

糖尿病(DM)可诱导内分泌和外分泌功能障碍，包括唾液腺损伤。尽管舌下腺(SLG)参与唾液分泌，但其在糖尿病中的作用仍研究不足。胍丁胺(AGM)是一种天然存在的多胺，具有抗氧化和抗炎特性；然而，其对糖尿病状态下舌下腺和胰腺的保护作用在很大程度上尚未被研究。本研究通过多层次分析，为糖尿病舌下腺损伤及AGM的剂量依赖性保护作用提供了新的见解。雄性Wistar大鼠通过单次腹腔注射链脲佐菌素(STZ，65 mg/kg)诱导糖尿病，并分别以低剂量(40 mg/kg)或高剂量(100 mg/kg)AGM治疗两周。采用组织学、免疫组织化学和生化方法分析舌下腺和胰腺。检测黏蛋白分泌(MUC-5B)，定量氧化应激标志物和促炎细胞因子，并使用H&E、阿利新蓝/过碘酸雪夫(Alcian Blue/PAS)及马洛里三色染色评估结构变化。免疫组织化学检测包括舌下腺的α-SMA和CK17以及胰腺的胰岛素受体。STZ诱导的糖尿病导致MUC-5B显著减少、氧化应激和促炎标志物升高、腺泡细胞和肌上皮细胞损伤以及胰腺β细胞损伤。胍丁胺给药以剂量依赖性方式改善这些指标，高剂量治疗恢复了黏蛋白分泌，调节了氧化和炎症指标，并维持了舌下腺和胰腺的组织学及免疫组织化学完整性。AGM通过抗氧化、抗炎和细胞保护机制，对糖尿病大鼠的舌下腺功能障碍和胰腺损伤发挥剂量依赖性保护作用。这些发现凸显了AGM在预防糖尿病唾液腺功能障碍和维持胰腺功能方面的治疗潜力。

Abstract

Diabetes mellitus (DM) induces endocrine and exocrine dysfunction, including salivary gland impairment. While the sublingual gland (SLG) contributes to saliva production, its involvement in diabetes remains understudied. Agmatine (AGM), a naturally occurring polyamine, exhibits antioxidant and anti-inflammatory properties; however, its protective effects on the SLG and pancreas in diabetes have remained largely uninvestigated. This study introduces new insights into SLG injury in diabetes and the dose-dependent protective benefits of AGM through multi-level analysis. Male Wistar rats were rendered diabetic by a single intraperitoneal STZ injection (65 mg/kg) and treated with either low-dose (40 mg/kg) or high-dose (100 mg/kg) AGM for two weeks. SLGs and the pancreas were analyzed by histological, immunohistochemical, and biochemical methods. Mucin secretion (MUC-5B) was measured, oxidative stress markers and pro-inflammatory cytokines were quantified, and structural changes were evaluated using H&E, Alcian Blue/PAS, and Mallory's trichrome staining. Immunohistochemistry included α-SMA and CK17 for SLG and insulin receptor for the pancreas. STZ-induced diabetes resulted in a substantial reduction in MUC-5B, increased oxidative stress and pro-inflammatory markers, damage to acinar and myoepithelial cells, and injury to pancreatic β-cells. Agmatine administration enhanced these parameters in a dose-dependent manner, with high-dose treatment reinstating mucin secretion, regulating oxidative and inflammatory indicators, and maintaining histological and immunohistochemical integrity in both the sublingual gland and pancreas. AGM confers dose-dependent protection against SLG dysfunction and pancreatic damage in diabetic rats via antioxidant, anti-inflammatory, and cytoprotective mechanisms. These findings highlight the therapeutic potential of AGM in preventing salivary gland dysfunction and maintaining pancreatic function in diabetes.

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