Influence of cilostazol on thromboangiitis obliterans in rats and the mechanism involved

Abstract

Purpose: To study the effect of Cilostazol on rat thromboangiitis obliterans (TAO), and the mechanism of action involved. Methods: Rats (N = 45) were injected with sodium laurate to establish the model of TAO, and then divided into Sham group (n = 15), TAO group (n = 15) and TAO + cilostazol group (n = 15). After administration of cilostazol, TAO lesions in the rats were graded, and the femoral arteries were stained by hematoxylin-eosin (H&E) to determine the degree of vascular lesions. The status of vascular endothelial cells was determined using transmission electron microscopy. Furthermore, the expression and transcription levels of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) proteins were evaluated by Western blotting and real-time polymerase chain reaction (RT-PCR) respectively. Results: In contrast to Sham group, TAO group exhibited symptoms such as changes in skin temperature and color, and limb swelling and thanatosis, while in the TAO + cilostazol group, the damage was reversed, vascular and vascular endothelial cell lesions were significantly ameliorated (p < 0.05), and the transcription and translation levels of HIF-1α and VEGF significantly suppressed (p < 0.05). Conclusion: Cilostazol alleviates sodium laurate-induced TAO lesions in rats via HIF-1α/VEGF pathway. This study may provide new insights for the treatment of TAO. Keywords: Cilostazol; Hypoxia-inducible factor/vascular endothelial growth factor pathway; Thromboangiitis obliterans; Limb swelling; Thanatosis