瑞舒伐他汀对动脉粥样硬化APOE^(-/-)小鼠VCAM-1、VEGF和TNF-α表达的影响  

Effect of Rosuvastatin on Expression of VCAM-1,VEGF and TNF-α in Atherosclerotic ApoE^(-/-) Mice

作　　者：张俊华 马永宾 苏建华 陈玉芳[2] 孙亚云 曹明 ZHANG Jun-hua(Department of Internal Neurology, Jintan Hospital Affiliated to Jiangsu University, Changzhou 213200, China)

机构地区：[1]江苏大学附属金坛医院神经内科 [2]常州市第四人民医院病理科,江苏常州213000

出　　处：《牡丹江医学院学报》2022年第3期20-24,33,共6页Journal of Mudanjiang Medical University

基　　金：金坛科技局科技项目(KJ201924)。

摘　　要：目的探讨瑞舒伐他汀对载脂蛋白E敲除基因(ApoE^(-/-))小鼠动脉粥样硬化的作用以及对血管细胞黏附分子-1(vascular cell adhesion molecule-1,VCAM-1)、血管内皮生长因子(vascular endothelial growth factor,VEGF)和α肿瘤坏死因子(tumor necrosis factor,TNF-α)表达的影响。方法将18只8周龄健康雄性ApoE^(-/-)小鼠随机分为3组,即模型组、低剂量治疗组和高剂量治疗组,每组6只,6只C57BL/6小鼠作为对照组;除对照组小鼠用普通饲料喂养外,3组ApoE^(-/-)小鼠均用高脂饲料喂养。喂养8周后,低剂量治疗组按瑞舒伐他汀1.5 mg/kg灌胃给药,高剂量治疗组按瑞舒伐他汀5 mg/kg灌胃给药,对照组和模型组用等量蒸馏水灌胃,1次/d,共8周;取胸主动脉HE染色后,观察主动脉的病理形态学变化,计算主动脉内弹力板周长、外弹力板周长、残腔周长和动脉粥样硬化斑块的面积;分别用蛋白质免疫印迹(Western Blot,WB)法和免疫组化法检测VCAM-1、VEGF和TNF-α在胸主动脉中的表达。结果ApoE^(-/-)小鼠用高脂饮食喂养后,主动脉根部可见显著的粥样硬化斑块。模型组的内弹力板周长较对照组明显增加,高剂量治疗组较模型组和低剂量治疗组明显降低(P<0.01);模型组的外弹力板周长较对照组明显增加,高剂量治疗组外弹力板周长较模型组和低剂量治疗组明显降低(P<0.01);模型组的残腔周长较对照组明显降低,低剂量治疗组和高剂量治疗组残腔周长均明显增加(P<0.01);低剂量治疗组和高剂量治疗组斑块面积较模型组缩小;高剂量治疗组斑块面积较低剂量治疗组缩小更明显(P<0.01);模型组VCAM-1、VEGF和TNF-α的相对灰度值较对照组升高(P<0.01),高剂量治疗组VCAM-1、VEGF和TNF-α的相对灰度值较模型组降低(P<0.01);模型组VCAM-1、VEGF、TNF-α光密度值较对照组升高(P<0.01);低剂量治疗组TNF-α光密度值较模型组降低(P<0.01);高剂量治疗组VCAM-1、VEGF和TNF-α光密度值较�Objective To investigate the effect of rosuvastatin on atherosclerosis and the expression of VCAM-1,VEGF and TNF-α in serum of ApoE^(-/-) mice.Methods Eighteen healthy 8-week-old male ApoE^(-/-) mice were randomly divided into 3 groups: model group, low-dose treatment group and high-dose treatment group, with 6 mice in each group. Six C57 BL/6 mice were used as control group. ApoE^(-/-) mice in the three groups were fed with high fat diet, and the control group was fed with standard diet. After 8 weeks of feeding, the low-dose treatment group was given rosuvastatin with 1.5 mg/kg, the high-dose treatment group with 5 mg/kg, and the control group and model group were given distilled water, once a day by gavage, for 8 weeks. After HE staining of thoracic aorta, the pathomorphological changes of aorta were observed, and the circumference of the elastic plate in the aorta, the circumference of the external elastic plate, the residual lumen and the area of atherosclerotic plaque were calculated. The expression of VCAM-1, VEGF and TNF-α in thoracic aorta was detected by Western Blot(WB) and immunohistochemistry. Results ApoE^(-/-) mice fed a high-fat diet showed significant atherosclerotic plaques in the aortic root. The girth of the internal elastic plate in the model group was significantly increased compared with that in the control group and significantly decreased in the high-dose treatment group compared with that in the model group and low-dose treatment group(P<0.01). Compared with the control group, the circumference of the external elastic plate in the model group was significantly increased, and was significantly decreased in the high-dose treatment group compared with the model group and the low-dose treatment group(P<0.01). The residual cavity circumference in the model group was significantly lower than that in the control group, and was significantly increased in the low-dose and high-dose groups(P<0.01). The plaque area of low-dose treatment group and high-dose treatment group was smaller than that of

关 键 词：瑞舒伐他汀 APOE^(-/-)小鼠 VCAM-1 VEGF TNF-Α 

分 类 号：R972[医药卫生—药品] R543.1[医药卫生—药学]