当归甙调控FOXO1 干预高血压模型大鼠的血管内皮功能障碍.

OBJECTIVE: To investigate whether sweroside regulates hypertension-induced vascular endothelial dysfunction by regulating Forkhead box O1 (FOXO1) expression. METHODS: (1) In vivo: The renal aorta constriction method was used to establish a hypertensive rat model. Forty male Sprague-Dawley rats were randomly divided into four groups: sham group, hypertension group, hypertension+25 mg/kg sweroside group, and hypertension+50 mg/kg sweroside group. TUNEL staining was used to detect the apoptosis of rat thoracic aorta endothelial cells. (2) In vitro: 50 μmol/L H2O2 was used to stimulate human umbilical vein endothelial cells to establish a cell oxidative damage model. Damaged cells were divided into control group, H2O2 group, H2O2+10, 20, or 40 μmol/L sweroside groups, H2O2+Vector group (negative control), H2O2+pcDNA-FOXO1 group, H2O2+40 μmol/L sweroside+Scramble group (negative control), and H2O2+40 μmol/L sweroside+si-FOXO1 group. MTT and flow cytometry were used to detect cell proliferation and apoptosis, respectively. ELISA was used to detect the levels of angiotensin II, malondialdehyde, and nitric oxide levels in rat serum and human umbilical vein endothelial cells, as well as vascular cell adhesion molecule 1, intercellular adhesion molecule 1, and E-selection levels in rat thoracic aorta tissues and human umbilical vein endothelial cells. RT-qPCR and western blot were used to detect the mRNA and protein expression of FOXO1 in rat thoracic aorta tissues and human umbilical vein endothelial cells. RESULTS AND CONCLUSION: (1) In vivo: compared with the sham group, blood pressure and apoptosis were significantly increased (P < 0.05), the expression levels of FOXO1 mRNA and protein were significantly reduced (P < 0.05), the contents of angiotensin II, malondialdehyde, vascular cell adhesion molecule 1, intercellular adhesion molecule 1, and E-selectin were significantly increased (P < 0.05), and the content of nitric oxide was significantly reduced (P < 0.05) in hypertensive rats. Sweroside could improve vascular dysfunction in hypertensive rats in a dose-dependent manner. (2) In vitro: compared with the control group, cell proliferation, FOXO1 expression and nitric oxide content were significantly reduced (P < 0.05), and cell apoptosis and malondialdehyde, vascular cell adhesion molecule 1, intercellular adhesion molecule 1, and E-selection contents were significantly increased (P < 0.05) in the H2O2 group. Sweroside treatment or FOXO1 overexpression could improve the dysfunction of human umbilical vein endothelial cells induced by H2O2, and the interference of FOXO1 could reverse the effect of sweroside. To conclude, sweroside can improve vascular endothelial dysfunction in hypertensive rats by promoting FOXO1 expression. [ABSTRACT FROM AUTHOR]