Scholarlink

Objective <p>This study investigates the therapeutic potential of low-molecular-weight heparin (LMWH) in acute pancreatitis (AP), focusing on its effects on lipid metabolism, inflammatory responses, and pancreatic tissue integrity. The study also explores the involvement of the PI3K/Akt pathway in mediating LMWH’s protective effects.</p> Methods <p>A rat model of AP was induced using L-arginine, followed by treatment with low-dose (100 IU/kg) or high-dose (500 IU/kg) LMWH. Serum biomarkers such as amylase, lipase, Alanine Aminotransferase(ALT), Aspartate Aminotransferase (AST), Interleukin-1 beta (IL-1β), Tumor Necrosis Factor-alpha (TNF-α), and lipid profiles were quantified using ELISA, while histopathological changes were evaluated through hematoxylin and eosin (HE) staining. Ultrastructural changes were observed via electron microscopy. The expression levels of Phosphatidylinositol 3-Kinase (PI3K), Phosphorylated Akt (p-Akt), sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS)were determined by Western blot and RT-qPCR analysis.</p> Results <p>LMWH treatment significantly reduced serum amylase and lipase levels, alleviated liver and kidney injury markers ALT, AST, Blood Urea Nitrogen (BUN), and Creatinine (CREA), and improved lipid profiles by lowering triglycerides (TG)and cholesterol (TC) while increasing HDL-C (<i>P</i> &lt; 0.05). The levels of inflammatory cytokines IL-1β and TNF-α were significantly lower in the LMWH-treated groups compared to the AP group (<i>P</i> &lt; 0.05). HE staining and electron microscopy revealed that LMWH preserved pancreatic tissue architecture and reduced acinar cell necrosis and mitochondrial damage. High-dose LMWH showed greater efficacy than low-dose treatment. LMWH downregulated the expression of lipid metabolism–related genes SREBP-1c and FAS, suggesting an inhibitory effect on lipogenesis. These effects might be driven by the activation of the PI3K/Akt signaling pathway.</p> Conclusion <p>LMWH ameliorates acute pancreatitis by mitigating pancreatic injury, suppressing inflammatory responses, and modulating lipid metabolism. These effects might be driven by the activation of the PI3K/Akt signaling pathway. LMWH holds promise as an adjunctive therapy for AP, warranting further exploration in clinical settings.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Low-molecular-weight heparin alleviates L-arginine-induced acute pancreatitis by modulating lipid metabolism and inflammatory responses in a rat model

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年9月26日

查看全文
  • Jianmei Zeng,
  • Kejin Li,
  • Limao Xu,
  • Chengfeng Wu,
  • Fei Wang,
  • Juan Huang

摘要

Objective

This study investigates the therapeutic potential of low-molecular-weight heparin (LMWH) in acute pancreatitis (AP), focusing on its effects on lipid metabolism, inflammatory responses, and pancreatic tissue integrity. The study also explores the involvement of the PI3K/Akt pathway in mediating LMWH’s protective effects.

Methods

A rat model of AP was induced using L-arginine, followed by treatment with low-dose (100 IU/kg) or high-dose (500 IU/kg) LMWH. Serum biomarkers such as amylase, lipase, Alanine Aminotransferase(ALT), Aspartate Aminotransferase (AST), Interleukin-1 beta (IL-1β), Tumor Necrosis Factor-alpha (TNF-α), and lipid profiles were quantified using ELISA, while histopathological changes were evaluated through hematoxylin and eosin (HE) staining. Ultrastructural changes were observed via electron microscopy. The expression levels of Phosphatidylinositol 3-Kinase (PI3K), Phosphorylated Akt (p-Akt), sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS)were determined by Western blot and RT-qPCR analysis.

Results

LMWH treatment significantly reduced serum amylase and lipase levels, alleviated liver and kidney injury markers ALT, AST, Blood Urea Nitrogen (BUN), and Creatinine (CREA), and improved lipid profiles by lowering triglycerides (TG)and cholesterol (TC) while increasing HDL-C (P < 0.05). The levels of inflammatory cytokines IL-1β and TNF-α were significantly lower in the LMWH-treated groups compared to the AP group (P < 0.05). HE staining and electron microscopy revealed that LMWH preserved pancreatic tissue architecture and reduced acinar cell necrosis and mitochondrial damage. High-dose LMWH showed greater efficacy than low-dose treatment. LMWH downregulated the expression of lipid metabolism–related genes SREBP-1c and FAS, suggesting an inhibitory effect on lipogenesis. These effects might be driven by the activation of the PI3K/Akt signaling pathway.

Conclusion

LMWH ameliorates acute pancreatitis by mitigating pancreatic injury, suppressing inflammatory responses, and modulating lipid metabolism. These effects might be driven by the activation of the PI3K/Akt signaling pathway. LMWH holds promise as an adjunctive therapy for AP, warranting further exploration in clinical settings.