Objective: To investigate the therapy effect of valsartan on oxidative stress and the formation of atherosclerosis of rabbit. Methods: An atherosclerotic rabbit model was established by feeding high cholesterol diet s...Objective: To investigate the therapy effect of valsartan on oxidative stress and the formation of atherosclerosis of rabbit. Methods: An atherosclerotic rabbit model was established by feeding high cholesterol diet supplemented by bovine serum albumin injection bolus. The rabbits were randomly divided into the control, model, and valsartan treated group, six rabbits in each group. Blood samples were collected at the end of 8 weeks for examination of serum lipid levels and MDA levels; the aortas were harvested for histological morphometry analysis, vascular cell adhesion molecule-1 (VCAM-1) immunohistochemical analysis and in situ superoxide detection to reflect the activity of NAD(P)H oxidase. Results: Rabbits fed with high cholesterol diet showed higher serum lipids levels than those fed with normal diet(P<0.01). Treatment with valsartan (10 mg/kg per day) did not alter serum lipids levels. But the serum MDA level and ratio of lesion to intima area reduced significantly compared with model group(P<0.05). The expression of VCAM-1 decreased significantly in the valsartan treated group than in the model group (P<0.05).In addition, in situ superoxide detection also show the markedly reduction of superoxide as a result of valsartan treatment. Conclusion: These results indicate that the valsartan treatment can reduce the atherosclerotic progression, the mechanisms of which may include the inhibiting the NAD(P)H oxidase activity to produce superoxide and the downregulating the expression of redox sensitive genes in the downstream, such as VCAM-1.展开更多
OBJECTIVE:To observe the effects of different doses of Wenxiao Ⅱ Decoction on the expression of monocyte chemoattractant protein-1(MCP-1) and vascular cell adhesion molecule-1(VCAM-1) in an experimental model of athe...OBJECTIVE:To observe the effects of different doses of Wenxiao Ⅱ Decoction on the expression of monocyte chemoattractant protein-1(MCP-1) and vascular cell adhesion molecule-1(VCAM-1) in an experimental model of atherosclerosis in rabbits and to explore the mechanism by which it alleviates atherosclerosis.METHODS:Sixty 3-4 month-old New Zealand rabbits of both sexes were randomly divided into six groups:simvastain;model;blank;and high-dose,mid-dose,and low-dose Wenxiao Ⅱ Decoction groups.Except for those in the blank group,all rabbits were fed a high-cholesterol diet.Carotid atherosclerosis was established by balloon-induced injury to the endothelium of the carotid artery in conjunction with consumption of a high-cholesterol diet.After 8 weeks,all rabbits were killed to evaluate the expression of MCP-1 and VCAM-1 by immunohistochemical staining.RESULTS:Expressions of MCP-1 and VCAM-1 were significantly decreased in all groups except the blank group compared with the model group(P<0.05).When compared with the simvastain group only variation of MCP-1 expression in low-dose group was not appreciable,and the differences were indistinct(P<0.05).When comparing among Wenxiao Ⅱ Decoction groups,MCP-1 expression in the mid-and high-dose groups was significantly lower than that seen in the low-dose group(P<0.01),but there were no differences among three dosage groups with respect to VCAM-1 expression(P>0.05).CONCLUSION:These data suggested that high,mid,and low doses of Wenxiao Ⅱ Decoction can inhibit the expression of MCP-1 and VCAM-1,which may prevent the formation of or stabilize atherosclerotic plaques.There may be a direct relationship between the dosage of Wenxiao Ⅱ Decoction and its therapeutic efficacy.展开更多
文摘Objective: To investigate the therapy effect of valsartan on oxidative stress and the formation of atherosclerosis of rabbit. Methods: An atherosclerotic rabbit model was established by feeding high cholesterol diet supplemented by bovine serum albumin injection bolus. The rabbits were randomly divided into the control, model, and valsartan treated group, six rabbits in each group. Blood samples were collected at the end of 8 weeks for examination of serum lipid levels and MDA levels; the aortas were harvested for histological morphometry analysis, vascular cell adhesion molecule-1 (VCAM-1) immunohistochemical analysis and in situ superoxide detection to reflect the activity of NAD(P)H oxidase. Results: Rabbits fed with high cholesterol diet showed higher serum lipids levels than those fed with normal diet(P<0.01). Treatment with valsartan (10 mg/kg per day) did not alter serum lipids levels. But the serum MDA level and ratio of lesion to intima area reduced significantly compared with model group(P<0.05). The expression of VCAM-1 decreased significantly in the valsartan treated group than in the model group (P<0.05).In addition, in situ superoxide detection also show the markedly reduction of superoxide as a result of valsartan treatment. Conclusion: These results indicate that the valsartan treatment can reduce the atherosclerotic progression, the mechanisms of which may include the inhibiting the NAD(P)H oxidase activity to produce superoxide and the downregulating the expression of redox sensitive genes in the downstream, such as VCAM-1.
基金Supported by Research Grant from the Health Bureau of Shanghai(No.2008J003A)
文摘OBJECTIVE:To observe the effects of different doses of Wenxiao Ⅱ Decoction on the expression of monocyte chemoattractant protein-1(MCP-1) and vascular cell adhesion molecule-1(VCAM-1) in an experimental model of atherosclerosis in rabbits and to explore the mechanism by which it alleviates atherosclerosis.METHODS:Sixty 3-4 month-old New Zealand rabbits of both sexes were randomly divided into six groups:simvastain;model;blank;and high-dose,mid-dose,and low-dose Wenxiao Ⅱ Decoction groups.Except for those in the blank group,all rabbits were fed a high-cholesterol diet.Carotid atherosclerosis was established by balloon-induced injury to the endothelium of the carotid artery in conjunction with consumption of a high-cholesterol diet.After 8 weeks,all rabbits were killed to evaluate the expression of MCP-1 and VCAM-1 by immunohistochemical staining.RESULTS:Expressions of MCP-1 and VCAM-1 were significantly decreased in all groups except the blank group compared with the model group(P<0.05).When compared with the simvastain group only variation of MCP-1 expression in low-dose group was not appreciable,and the differences were indistinct(P<0.05).When comparing among Wenxiao Ⅱ Decoction groups,MCP-1 expression in the mid-and high-dose groups was significantly lower than that seen in the low-dose group(P<0.01),but there were no differences among three dosage groups with respect to VCAM-1 expression(P>0.05).CONCLUSION:These data suggested that high,mid,and low doses of Wenxiao Ⅱ Decoction can inhibit the expression of MCP-1 and VCAM-1,which may prevent the formation of or stabilize atherosclerotic plaques.There may be a direct relationship between the dosage of Wenxiao Ⅱ Decoction and its therapeutic efficacy.
