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氯沙坦对大鼠动脉粥样硬化的影响
郭延松1*,吴宗贵1,杨军柯3,林皓平1
0
(1. 福建医科大学省立临床医学院, 福建省立医院心血管内科,福州 350001
2. 第二军医大学长征医院心血管内科,上海 200003
3. 解放军第二炮兵总医院心血管内科,北京 100088
*通信作者)
摘要:
目的研究氯沙坦对大鼠动脉粥样硬化的影响。方法Wistar雄性大鼠30只,随机分为正常对照组、动脉粥样硬化模型组和氯沙坦治疗组,正常组喂基础饲料,模型组以高脂饲料+维生素D3+动脉内膜球囊损伤术建立动脉粥样硬化模型,治疗组同法造模后加氯沙坦治疗。喂养90 d后,比较各组间血脂水平、血钙水平、胸主动脉形态学改变、巨噬细胞和α-平滑肌肌动蛋白免疫组织化学结果、血浆和胸主动脉血管紧张素Ⅱ(AngⅡ)水平。分析病变部位的AngⅡ水平与相应的内膜厚度的相关性。结果与对照组相比,模型组和治疗组总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、血钙水平均升高,差异有统计学意义(P<0.01);模型组与对照组相比,内膜厚度增厚,中层厚度变薄(P<0.01);治疗组与模型组相比,内膜厚度变薄,中层厚度变厚(P<0.01)。对照组CD68阴性,模型组强阳性,治疗组为弱阳性;模型组斑块表面只有很薄的一层α-平滑肌肌动蛋白阳性,中层明显萎缩;治疗组内膜及中层均有较厚的α-平滑肌肌动蛋白阳性。血浆AngⅡ水平在3组间无差别;胸主动脉组织中的AngⅡ水平在模型组及治疗组均较对照组升高(P<0.01),治疗组较模型组降低(P<0.05)。主动脉粥样硬化病变中AngⅡ水平与相应的内膜厚度呈正相关。结论氯沙坦有抗动脉粥样硬化作用。
关键词:  氯沙坦  动脉粥样硬化  血管紧张素Ⅱ
DOI:10.3724/SP.J.1008.2011.01286
投稿时间:2011-09-05修订日期:2011-12-06
基金项目:
Effect of lorsartan on rat model of atherosclerosis
GUO Yan-song1*,WU Zong-gui1,YANG Jun-ke3,LIN Hao-ping1
(1. Department of Cardiovasology, Clinical Medical College of Fujian Medical University, Provincial Hospital of Fujian, Fuzhou 350001, Fujian, China
2. Department of Cardiovasology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
3. Department of Cardiovasology, General Hospital, Second Artillery Brigade of PLA, Bejing 100088, China
*Corresponding author.)
Abstract:
ObjectiveTo investigate the effect of lorsartan on rat model of atherosclerosis. MethodsTotally 30 male Wistar rats were randomly divided to three different groups: control group, model group(high lipid+Vitamin D overload+endothelium injury), and treatment group(high lipid+Vitamin D overload+endothelium injury+lorsartan). Rat model of atherosclerosis was established by high lipid plus Vitamin D overload plus baloon angioplasty-induced endothelium injury, and animals in the treatment group were models treated with lorsartan. After 90 days the blood samples were drawn to examine the serum lipids and calcium, H-E staining was used to observe the structure changes of thoracic aorta, and immunohistochemistry assay was used to observe CD68 and α-actin expression in the thoracic aorta. To study the relationship between AngⅡ and severity of AS, radio-immunity analysis was used to assay AngⅡ in each group,with the thickness of intima used as the index of AS severity. ResultsThe serum levels of total cholesterol (TC), triglyceride (TG), LDL-C and serum calcium in model and treatment groups were significantly higher than those in the control group (P<0.01). Compared with the control group, the model group had a thicker intima and thinner media. Compared with model group, the treatment group had a significantly thinner intima and thicker media (P<0.01). Immunohistochemistry showed that CD68 was negative in the control group, strongly positive in the model group and weakly positive in the treatment group. Compared with model group, α-actin positive level was higher in the treatment group. The serum AngⅡ levels were not significantly different between the three groups. AngⅡ level in the thoracic aorta tissue in the treatment group was significantly lower than that in control group and higher than that in the model group (P<0.05). AngⅡ level in the thoracic aorta tissue was positively related with the intima thickness (P<0.01). ConclusionLorsartan has anti-atherosclerosis effect in rats.
Key words:  lorsartan  atherosclerosis  angiotensin Ⅱ