College of Pharmacy, Xinxiang Medical University, Xinxiang, China.
School of Basic Medical Science, Xinxiang Medical University, Xinxiang, China,
Pharmacology. 2020;105(9-10):531-540. doi: 10.1159/000504758. Epub 2020 Apr 7.
Atherosclerosis (AS) is a chronical pathological process of the arterial narrows due to the AS plaque formation. The aim of this study was to explore the therapeutic effect and the underlying mechanism of Floralozone on experimental atherosclerotic model rats. Experimental atherosclerotic model rats were induced by the right carotid artery balloon injury and intraperitoneal injection of vitamin D3 in rats after 4 weeks high-fat diet. The results exhibited that Floralozone could ameliorate vascular injury and vasorelaxation of descending aortas and increase the superoxide dismutase activity and the expression of sphingosine 1-phosphate (S1P) 1 and reduce the intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, interleukin (IL)-1, IL-6 level, and the malondialdehyde activity in experimental atherosclerotic rats. However, Fingolimod, an S1P1 inhibitor, could reverse these Floralozone effects in experimental atherosclerotic rats. Our results indicated that Floralozone could inhibit the atherosclerotic plaque formation and improves arterial stenosis and reduces endothelial dysfunction in experimental atherosclerotic rats, which might be involved with S1P1 enhancement.
动脉粥样硬化(AS)是由于 AS 斑块形成导致动脉狭窄的慢性病理过程。本研究旨在探讨 Floralozone 对实验性动脉粥样硬化模型大鼠的治疗作用及作用机制。采用右侧颈总动脉球囊损伤联合腹腔注射维生素 D3 建立大鼠高脂饮食 4 周后的实验性动脉粥样硬化模型。结果表明,Floralozone 可改善实验性动脉粥样硬化大鼠的血管损伤和血管舒张功能,增加超氧化物歧化酶活性和鞘氨醇 1-磷酸(S1P)1 的表达,降低细胞间黏附分子-1、血管细胞黏附分子-1、白细胞介素(IL)-1、IL-6 水平和丙二醛活性。然而,S1P1 抑制剂 fingolimod 可逆转 Floralozone 对实验性动脉粥样硬化大鼠的这些作用。我们的研究结果表明,Floralozone 可抑制动脉粥样硬化斑块形成,改善实验性动脉粥样硬化大鼠的动脉狭窄和内皮功能障碍,这可能与 S1P1 的增强有关。