BACKGROUND The present study was aimed to explore the effects and the underlying mechanism of prophylactic low-molecular-weight heparin (LMWH) treatment on taurocholate-induced severe acute pancreatitis (SAP) in a rat model. METHODS Rat SAP model was induced by injection of 4% sodium taurocholate into the pancreatic duct. LMWH was applied half an hour before the induction of pancreatitis at the dose of 200 IU/kg subcutaneous injection. The rats were euthanized at 1 h, 6 h, and 12 h after taurocholate-induced SAP. The inflammatory and oxidative response markers were assessed. And the vascular endothelial growth factor (VEGF) and Fms-related tyrosine kinase 1 (Flt-1) expression were evaluated by immunohistochemistry (IHC) and western blot methods. RESULTS The expression of inflammatory and oxidative response markers increased after induction of SAP. IHC and western blot results showed the VEGF and Flt-1 expression were increased in SAP group. Prophylactic LMWH administration reduced the inflammatory and oxidative response markers expression and decreased the expression of VEGF and Flt-1. CONCLUSIONS This study suggested that prophylactic LMWH treatment mitigated the severity of pancreatitis in rat SAP model by anti-inflammation and oxidative response. The underlying mechanism may result from downregulating VEGF/Flt-1 signaling of LMWH in SAP rat model.

中文翻译：

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在大鼠模型中，通过 VEGF/Flt-1 信号传导部分预防性低分子量肝素给药可预防严重急性胰腺炎。

背景本研究旨在探讨预防性低分子肝素（LMWH）治疗对牛磺胆酸盐诱导的大鼠重症急性胰腺炎（SAP）的影响及其潜在机制。方法通过胰管内注射4%牛磺胆酸钠诱导大鼠SAP模型。在诱发胰腺炎前半小时应用 LMWH，剂量为 200 IU/kg 皮下注射。在牛磺胆酸盐诱导的 SAP 后 1 小时、6 小时和 12 小时对大鼠实施安乐死。评估炎症和氧化反应标志物。并通过免疫组织化学（IHC）和蛋白质印迹法评估血管内皮生长因子（VEGF）和Fms相关酪氨酸激酶1（Flt-1）的表达。结果SAP诱导后炎症和氧化反应标志物的表达增加。IHC和western blot结果显示SAP组VEGF和Flt-1表达增加。预防性LMWH给药降低了炎症和氧化反应标志物的表达，并降低了VEGF和Flt-1的表达。结论 本研究表明，预防性 LMWH 治疗通过抗炎和氧化反应减轻了大鼠 SAP 模型中胰腺炎的严重程度。潜在机制可能是由于在 SAP 大鼠模型中下调 LMWH 的 VEGF/Flt-1 信号传导。预防性LMWH给药降低了炎症和氧化反应标志物的表达，并降低了VEGF和Flt-1的表达。结论 本研究表明，预防性 LMWH 治疗通过抗炎和氧化反应减轻了大鼠 SAP 模型中胰腺炎的严重程度。潜在机制可能是由于在 SAP 大鼠模型中下调 LMWH 的 VEGF/Flt-1 信号传导。预防性LMWH给药降低了炎症和氧化反应标志物的表达，并降低了VEGF和Flt-1的表达。结论 本研究表明，预防性 LMWH 治疗通过抗炎和氧化反应减轻了大鼠 SAP 模型中胰腺炎的严重程度。潜在机制可能是由于在 SAP 大鼠模型中下调 LMWH 的 VEGF/Flt-1 信号传导。