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.