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

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. 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. 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. 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.