【作者】 刘锦秀；

【导师】 陈还珍；

【作者基本信息】 山西医科大学 ， 心血管内科学， 2010， 硕士

【摘要】 目的：通过建立动脉粥样硬化的大鼠模型,观察坎地沙坦西酯对大鼠主动脉粥样硬化的作用,及对MCP-1、CRP含量的影响,从而观察坎地沙坦西酯的抗炎作用。方法：选取30只健康的雄性Wistar大鼠,随机分为3组,正常对照组(NC)、高脂对照组(HC)、坎地沙坦西酯组(HC+C),分别饲养8周。①血脂测定：分别于实验前及8周末采血,用化学法测定血清血脂水平；②血清hs-CRP测定：分别于实验前及8周末取大鼠血清,用酶联免疫吸附试验(ELISA法)检测大鼠血清中的hs-CRP含量变化；③大鼠主动脉病理形态观察：饲养8周末,大鼠麻醉后迅速开胸,分离胸主动脉,固定、切片、脱水及HE染色,光镜下观察主动脉形态并拍照；④胸主动脉MCP-1蛋白的表达：分离的主动脉进行石蜡固定、切片、脱水,免疫组织化学法染色,光镜下观察主动脉MCP-1蛋白的表达情况并照相,用病理图像分析系统测定平均灰度值,并进行比较。结果：①实验前各组大鼠血脂水平相似(P>0.05)；8周末,HC组及HC+C组大鼠TG、TC、LDL-C较NC组明显升高(P<0.01),HC组与HC+C组相比较,差异不大,无统计学意义(P>0.05)。②实验前各实验组大鼠hs-CRP含量相似,无显著性差异(P>0.05)。8周末,HC组大鼠hs-CRP含量较NC组明显升高(P<0.01), HC+C组大鼠,显著降低hs-CRP含量(P<0.01)。③HC组大鼠主动脉内膜增厚,中膜可见平滑肌纤维排列紊乱,外膜炎症细胞浸润,HC+C组介于NC组及HC组之间,内膜轻度增厚、外膜少量炎细胞浸润。④各实验组MCP-1蛋白表达阳性表现呈棕黄色颗粒,位于胞膜及胞浆内,主要见于新生内膜,中膜亦有表达。NC组及HC+C组平均灰度值(分别为156.94±8.158、130.98±5.941)明显高于HC组(123.74±5.616)(P<0.01)。结论：①坎地沙坦西酯不影响AS大鼠的血脂水平；②坎地沙坦西酯有抗炎作用,使hs-CRP及MCP-1水平降低；③坎地沙坦西酯可能延缓AS的进程。更多还原

【Abstract】 Objective:This study sought to investigate the effect of candesartan on the expression of monocyte chemoattractant protein-1, high-sensitivity C-reactive protein and so on, in order to examining the effect of candesartan on the formation of atherosclerosis.Method:There is thirty male wistar rats that were randomly divided into three groups, each group had ten:normal control group (NC)、high-cholesterol control group (HC)、high-cholesterol+candesartan group (HC+C),the rats were fed for eight weeks.①The concentrations of lipid in plasma were measured by chemical method at 0-week、8-week respectively, compared with the control group.②Collected the blood at 0-week and 8-week respectively, detected with enzyme-linked immunosorbent assay(ELISA), compared with each other.③The rats for 8-week feeding,anesthesia, rapid thoracotomy, aortic isolated, fixed, sliced, dehydrated, and HE staining, observed artery intima-media thickness under light microscope, and photoed.④Detected expression of MCP-1 by immunohistochemistry, calculated the average gray value, and compared.Results:①Candesartan cilexetil on the levels of lipid in atherosclerotic rats:before experiment, the lipid levels in plasma were similar among each groups, there was no significant difFerence(P>0.05);At the end of 8 weeks, concentrations of lipid in HC and HC+C group were significantly higher than that in NC group(P<0.01),there was no difference between HC and HC +C group(P>0.05).②Observed changes in hs-CRP in each group:before the experiment the levels of hs-CRP were similar among each groups, there was no significant difference(P>0.05). After 8 weeks, the concentrations of hs-CRP in HC group were significantly higher than that in HC+C group (P<0.01).③The effect of candesartan on arterial intima-media thickness:the arterial intima-media in HC group was thicker than the others, muscle fibers can be seen in the disordered membrane, inflammatory cell infiltrated outer membrane. In HC+C group than in HC group with mild intimal thickening, adventitial small infiltration of inflammatory cells.④The effect of candesartan on expression of MCP-1:MCP-1 protein expression showed a positive brown particles in the membrane and the cytoplasm, mainly seen in the neointima, also expressed in the membrane. The average gray value in NC and HC+C group(respectively, 156.94±8.158、130.98±5.941) was significantly higher than that in HC group(123.74±5.616) (P<0.01)Conclusion:①Candesartan can’t reduce the lipid levels.②Candesartan can lower the expression of MCP-1 and hs-CRP, so candesartan cilexetil have anti-inflammatory effects.③Candesartan cilexetil maybe delay the process of atherosclerosis.更多还原