槲皮素调节SDF-1/CXCR4轴对下肢动脉硬化闭塞症大鼠的治疗作用

Therapeutic Effect of Quercetin on Rats with Arteriosclerosis Occlusive Disease of the Lower Extremities by Regulating SDF-1/CXCR4 Axis

关键词:  槲皮素  下肢动脉硬化闭塞症  大鼠  治疗  基质细胞衍生因子-1/CXC型趋化因子受体

Key words:  quercetin  arteriosclerosis occlusive disease of the lower extremities  rat  treatment  stromal cell-derived factor-1/CXC chemokine receptor上

摘要:

目的 探究槲皮素调节基质细胞衍生因子-1(stromal cell-derived factor-1，SDF-1)/CXC型趋化因子受体4(CXC chemokine receptor-4，CXCR4)轴对下肢动脉硬化闭塞(arteriosclerosis occlusive disease of the lower extremities，ASOLE)大鼠的治疗作用。方法 取SD大鼠制备ASOLE模型48只，随机分为模型组、槲皮素低剂量(10 mg·kg^-1)组、槲皮素高剂量(20 mg·kg^-1)组、槲皮素(20 mg·kg^-1)+AMD3100(2.5 mg·kg^-1)组，另选12只大鼠做假手术组，药物干预后检测大鼠血脂三酰甘油(triglyceride，TG)、胆固醇(cholesterol，TC)水平；HE、EVG染色检测大鼠动脉血管组织病理形态改变，激光散斑血流成像系统检测下肢动脉血流速度；ELISA测定大鼠血清内皮素(serum endothelin，ET-1)、细胞间黏附分子-1(intercellular adhesion molecule-1，ICAM-1)、血管细胞黏附蛋白-1(vascular cell adhesion protein-1，VCAM-1)水平及促炎因子肿瘤坏死因子-α(tumor necrosis factor-α，TNF-α)、环氧化酶-2(cyclooxygenase-2，COX-2)、白细胞介素-17(interleukin-17，IL-17)水平；蛋白免疫印迹试验检测大鼠动脉血管组织SDF-1及CXCR4蛋白表达。结果 与假手术组相比，模型组大鼠动脉血管组织发生明显病理损伤改变，血清TG、TC、ET-1、ICAM-1、VCAM-1、TNF-α、COX-2、IL-17水平显著升高(P<0.05)，平均血流速度、SDF-1及CXCR4蛋白表达水平显著降低(P<0.05)；与模型组相比，槲皮素高、低剂量组大鼠动脉血管组织病理损伤减轻，血清TG、TC、ET-1、ICAM-1、VCAM-1、TNF-α、COX-2、IL-17水平降低(P<0.05)，平均血流速度、SDF-1及CXCR4蛋白表达水平升高(P<0.05)；与槲皮素低剂量组相比，槲皮素高剂量组大鼠动脉血管组织病理损伤减轻，血清TG、TC、ET-1、ICAM-1、VCAM-1、TNF-α、COX-2、IL-17水平降低(P<0.05)，平均血流速度、SDF-1及CXCR4蛋白表达水平升高(P<0.05)；与槲皮素高剂量组相比，槲皮素+AMD3100组大鼠动脉血管组织病理损伤加重，血清TG、TC、ET-1、ICAM-1、VCAM-1、TNF-α、COX-2、IL-17水平升高(P<0.05)，平均血流速度、SDF-1及CXCR4蛋白表达水平均降低(P<0.05)。结论 槲皮素可激活SDF-1/CXCR4信号，抑制炎症，改善血脂代谢，减轻ASOLE模型大鼠动脉血管组织损伤，保护血管内皮功能。

Abstract:

OBJECTIVE To explore the therapeutic effect of quercetin on rats with arteriosclerosis occlusive disease of the lower extremities(ASOLE) through regulating stromal cell-derived factor-1(SDF-1)/CXC chemokine receptor-4(CXCR4) axis. METHODS Forty-eight ASOLE model rats were prepared from SD rats. They were divided into model group, quercetin low dose(10 mg·kg^-1) group, quercetin high dose(20 mg·kg^-1) group, and quercetin(20 mg·kg^-1)+AMD3100(2.5 mg·kg^-1) group, another 12 rats were selected as sham operation group. After treated with drugs in groups, the blood lipid levels of triglyceride (TG), cholesterol(TC) in the rats were detected. HE, EVG staining were conducted to detect the pathological and morphological changes of rat arteries and blood vessels, the mean blood flow velocity was detected by laser speckle blood flow imaging system. ELISA was used to measure the levels of serum endothelin(ET-1), intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion protein-1(VCAM-1) and levels of pro-inflammatory factors tumor necrosis factor-α(TNF-α), cyclooxygenase-2(COX-2), interleukin-17(IL-17). Western blotting was performed to detect the expression of SDF-1 and CXCR4 proteins in rat arterial tissues. RESULTS Compared with the sham operation group, the arterial vascular tissue of rats in the model group had obvious pathological changes, the levels of serum TG, TC, ET-1, ICAM-1, VCAM-1, TNF-α, COX-2, and IL-17 were significantly increased(P<0.05), and the mean blood flow velocity, the protein expression levels of SDF-1 and CXCR4 were significantly decreased(P<0.05). Compared with the model group, the pathological damage of the arterial tissues of the quercetin high and low dose group was reduced, the levels of serum TG, TC, ET-1, ICAM-1, VCAM-1, TNF-α, COX-2, and IL-17 were decreased(P<0.05), and the mean blood flow velocity, the protein expression levels of SDF-1 and CXCR4 were significantly increased(P<0.05). Compared with the quercetin low dose group, the pathological damage of the arterial tissues of the quercetin high dose group was reduced, the levels of serum TG, TC, ET-1, ICAM-1, VCAM-1, TNF-α, COX-2, and IL-17 were decreased(P<0.05), and the mean blood flow velocity, the protein expression levels of SDF-1 and CXCR4 were significantly increased(P<0.05). Compared with quercetin high dose group, the pathological damage of arterial and vascular tissues of the quercetin+AMD3100 group was aggravated, the levels of serum TG, TC, ET-1, ICAM-1, VCAM-1, TNF-α, COX-2, and IL-17 were increased(P<0.05), and the mean blood flow velocity, the protein expression levels of SDF-1 and CXCR4 were decreased(P<0.05). CONCLUSION Quercetin can activate SDF-1/CXCR4 signal, inhibit inflammation, improve blood lipid metabolism, reduce arterial tissue damage in ASOLE model rats, and protect their vascular endothelial function.