Fei Jianwen, Qin Xiao, Ma Hongfu, Zhang Xuefeng, Wang Haixia, Han Jin, Yu Chaoxiao, Jiang Junjie
Pulmonary and Critical Care Medicine, Yantaishan Hospital, Yantai, 264000, China.
Department of Orthopedics, Yantaishan Hospital, Laishan District, 10087 Keji Avenue, Yantai, 264000, No, China.
Inflammation. 2022 Dec;45(6):2268-2279. doi: 10.1007/s10753-022-01689-y. Epub 2022 Jun 2.
Deep vein thrombosis (DVT) has become a prevalent and increasingly serious problem globally and resveratrol (Res) is a natural antitoxin that inhibits arterial thrombosis. To investigate the effect of Res on DVT and further explore its mechanism, thrombosis was monitored at different time points and the pathological changes occurring in the inferior vena cava (IVC) and lung tissue were observed in Sprague-Dawley rats. The protein expression of HIF-1α and NLRP3 in the IVC and lung tissue and the concentrations of D-dimer (D2D), prothrombin fragment 1 + 2 (F1 + 2), interleukin-1β (IL-1β), caspase-1, and tissue factor (TF) in the plasma were determined. After setting different doses of Res groups and using low-molecular-weight heparin (LMWH) as a positive control to determine the effective experimental dose of Res, rats were further divided into sham, DVT, HIF-1α inhibitor, Res, and HIF-1α inhibitor + Res groups. The above indicators were tested repeatedly. The DVT was formed on the 1st day of modeling. With the extension of time, DVT was gradually institutionalized and finally recanalized. Lesions in the IVC and lung tissue were effectively ameliorated, and thrombosis was significantly decreased in the LMWH or 60 mg/kg Res-treated groups. The levels of D2D, F1 + 2, IL-1β, caspase-1, TF, and the expression of HIF-1α and NLRP3 were significantly reduced in the HIF-1α inhibitor, Res, and HIF-1α inhibitor + Res groups. Res can ameliorate DVT in rats by inhibiting HIF-1α/NLRP3 pathway, which provides a novel therapeutic strategy for DVT treatment.
深静脉血栓形成（DVT）已成为全球范围内普遍且日益严重的问题，而白藜芦醇（Res）是一种抑制动脉血栓形成的天然抗毒素。为了研究Res对DVT的影响并进一步探索其作用机制，在不同时间点监测Sprague-Dawley大鼠的血栓形成情况，并观察其下腔静脉（IVC）和肺组织发生的病理变化。测定IVC和肺组织中HIF-1α和NLRP3的蛋白表达以及血浆中D-二聚体（D2D）、凝血酶原片段1+2（F1+2）、白细胞介素-1β（IL-1β）、半胱天冬酶-1和组织因子（TF）的浓度。在设定不同剂量的Res组并使用低分子量肝素（LMWH）作为阳性对照以确定Res的有效实验剂量后，将大鼠进一步分为假手术组、DVT组、HIF-1α抑制剂组、Res组和HIF-1α抑制剂+Res组。对上述指标进行重复检测。建模第1天形成DVT。随着时间延长，DVT逐渐机化，最终再通。LMWH或60mg/kg Res治疗组可有效改善IVC和肺组织的病变，显著减少血栓形成。HIF-1α抑制剂组、Res组和HIF-1α抑制剂+Res组中D2D、F1+2、IL-1β、半胱天冬酶-1、TF的水平以及HIF-1α和NLRP3的表达均显著降低。Res可通过抑制HIF-1α/NLRP3通路改善大鼠DVT，为DVT治疗提供了一种新的治疗策略。
