摘要
目的探讨血管紧张素受体阻断剂缬沙坦的抗动脉粥样硬化的作用及其可能的作用机制。方法将30只健康雄性Wistar大鼠(体重220～250 g),随机分为正常对照组、动脉硬化组和缬沙坦组,每组10只。正常对照组行假球囊损伤手术给予正常饮食,余2组每只大鼠给予30万u/kg体重维生素D3右下肢肌肉注射后用球囊行动脉拉伤,在基础饲料中加入2%胆固醇、0.5%胆酸钠、0.2%丙基硫氧嘧啶、维生素D3粉剂(1.25×106u/kg饲料)、3%猪油等饲养。缬沙坦组同时给予缬沙坦30 mg/kg体重,1次/d灌胃。喂养9周后空腹24h抽血并处死,检测血脂水平,自主动脉弓下约1 cm处留取动脉组织1 cm用4%甲醛溶液固定,行HE染色,用免疫组化法检测斑块中AT1R和MCP-1蛋白的表达。结果动脉硬化组均形成了典型的粥样斑块;免疫组化半定量分析法表明:动脉硬化组与正常对照组及缬沙坦组比较,AT1R和MCP-1表达均明显升高(P<0.001);缬沙坦组MCP-1蛋白表达亦高于与正常对照组(P<0.05),而AT1R的表达两组间无统计学差异。结论缬沙坦通过拮抗AT1R从而抑制了MCP-1表达起到抗AS的作用。
【Objective】 To investigate the effects and mechanisms of valsartan on the expression of MCP-1 in rat atheromatous plaque.【Methods】 30 healthy male Wistar rats（220～250 g） were randomly divided into 3 groups with 10 rats each： normal control group,atherosclerosis group and Valsartan group.The rats in the normal control group were given a fake sacculus proprius damage operation and a normal diet.The rats in the other two groups were given a vitamin D3（3×105 u/kg feed） through intramuscular injection firstly.Then they were suffered from an artery strain by sacculus proprius and were administrated with a diet including 2% cholesterol,sodium cholate,0.2% PTU,vitamin D3（1.25×106 u/kg feed） and 3% lard.The rats in the valsartan group were given valsartan 30mg/kg by intragastric gavage once every day.After nine weeks,serum lipid levels of all the rats were detected after haemospasia on empty stomach and then killed.The slices was done at about 1cm below the aortic arch and the arteries were fixed by 0.4% formaldehyde solution immediately,the expressions of AT1R and MCP-1 in the vascular tissues were detected by immunohistochemistry method.【Results】 The rats in the arteriosclerosis group formed typical atheromatous plaque;The semiquantitative method of immunohistochemistry indicated that the expressions of AT1R and MCP-1 in the arteriosclerosis group were significantly higher than that in the normal control and Valsartan group（P 0.001）;The expression of MCP-1 in the valsartan group was significantly higher than that in the normal control group（P 0.05）.【Conclusions】 Valsartan can suppress the expression of MCP-1 by the antagonism of the AT1 receptor and inhibit the formation of arteriosclerosis.
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2011年第31期3861-3865,共5页
China Journal of Modern Medicine
