【作者】 刘莉；

【导师】 周玉娟；

【作者基本信息】 河北大学 ， 药理学， 2011， 硕士

【摘要】 目的:本研究通过建立大鼠动脉粥样硬化病理模型,观察坎地沙坦对动脉粥样硬化的干预作用,并探讨其可能的作用机制。方法:雄性、10周龄SD大鼠,随机分为5组:正常组(A组)、模型组(B组)、坎地沙坦低(1 mg.kg-1.d-1,C组)、中(5 mg.kg-1.d-1,D组)、高(10 mg.kg-1.d-1,E组)剂量组。B、C、D、E组均饲喂高脂饲料,配合一次性腹腔注射维生素D3建立大鼠AS模型。A组饲喂普通饲料,腹腔注射等体积生理盐水。坎地沙坦干预组自造模第一天开始灌胃,A、B组给予等量生理盐水灌胃饲养12周。光镜下HE染色观察腹主动脉病理改变,透射电镜下观察超微结构的改变。腹腔静脉取血,生化方法检测血脂、MDA、SOD、酶联免疫吸附双抗体夹心方法检测oxLDL。免疫组织化学的方法检测腹主动脉MMP-2、VEGF的表达。结果:1、B组血清TG水平高于A组,HDL水平低于A组(P<0.01)。C、D、E组血清TG水平均比B组下降(P<0.05,P<0.01),但三组间无差别(P>0.05),E组HDL比B组显著升高(P<0.01)。对于TG / HDL来说B组显著高于A组(P<0.05),E组较B组显著下降(P<0.05);C、D组较B组有所下降但差异无统计学意义(P>0.05)。2、模型组与正常组相比主动脉出现动脉粥样硬化的形态学改变;与模型组相比坎地沙坦低、中、高剂量组动脉粥样硬化的形态学改变有所减轻。3、B组大鼠血清MDA水平高于A组,两者差异有统计学意义(P<0.01);C、D组血清中MDA水平比B组降低,但差异没有统计学意义(P>0.05);E组能明显降低大鼠血清中MDA水平,与B组相比,差异有统计学意义(P<0.01)。B组大鼠血清SOD水平低于A照组,两者差异有统计学意义(P<0.01);E组能明显升高大鼠血清中SOD水平,与B组相比,差异有统计学意义(P<0.05)。4、血清oxLDL水平(ng/dl)B组大鼠高于A组,差异有统计学意义(P<0.01)。C组、D组、E组的血清oxLDL水平与B组相比明显降低,差异有统计学意义(P<0.01)。但C、D、E组之间无差别(P>0.05)。5、血管MMP-2的表达:D、E组较B组均减少(P<0.05);但B、C组间无差别(P>0.05),D、E组间无差别(P>0.05)。血管VEGF的表达:C、D、E组较B组均减少(P<0.05);D、E组较C组减少(P<0.05),但D、E组间无差别(P>0.05)。结论:1、坎地沙坦可以调节AS大鼠的血脂紊乱并减轻AS大鼠主动脉病理改变。2、坎地沙坦可以降低AS大鼠血清MDA水平、升高SOD水平;而且可以降低大鼠血清中的oxLDL水平。3、坎地沙坦通过减少AS大鼠血管MMP-2、VEGF的表达改善AS发生过程中血管的重塑。更多还原

【Abstract】 Objects:To investigate the anti-atherosclerosis effects and mechanism of Candesartan on experimental atherosclerosis rats.Methods:Male SD rats of ten-months were randomly divided into 5 groups:A(normal rats),B(atherosclerosis rats),C(atherosclerosis rats fed with candesartan 1 mg.kg-1.d-1), D(atherosclerosis rats fed with candesartan 5 mg.kg-1.d-1) and E(atherosclerosis rats fed with candesartan 10mg.kg-1.d-1). The rats of group B,C,D,E were fed with high lipid feedstuff and received intraperitoneal injection of vitamin D3 at one time. The rats of group A were fed with nomal feedstuff and injected the saline with the same dose. Candesartan was given to the rats of group C,D,E by gavage from the beginning to the end of the experiment. At the same time rats of groupA and B were given the saline of same dose by gavage. After 12 weeks,the same arteries of rats of each group were examined by HE staining and electron microscope.The lipid indexes, MDA and SOD were determined by biochemistry method.OxLDL in serum of each group rats was measured by ELISA. The expressions of MMP-2 and VEGF in aorta were determined by immunohistochemistry.Result:1 The TG in groupC,D and E was lower than those in group B without a dose-dependent manner(P<0.05,P<0.01).Compared with groupB,HDL increased significantly( P< 0. 05) in the group E. The TG / HDL in the group E decreased significantly( P< 0. 05).2 Compared with groupA, morphological changes of Atherosclerosis in the arteries of group B were observed.Compared with group B, morphological changes of atherosclerosis of groupC,D and E lightened significantly.3 Compared with group A,the MDA and SOD were significantly different in the group B ( P<0.01).The MDA in group E was lower than those in the group B ( P<0.01).Compared with group B, SOD increased significantly( P< 0. 05) in the group E.4 The oxLDL in groups of C,D and E were lower than those in group B without a dose- dependent manner(P<0.01).5 Compared with group B, the expressions of MMP-2 in aorta decreased in groups of D and E(P<0.05). Compared with group B, the expressions of VEGF in aorta decreased in groups of C,D and E(P<0.05).Conclusion:1 Candesartan can regulate the disorder of blood lipids and influence the morphology of artery in atherosclerosis rats.2 Candesartan can increase SOD and decrease MDA and oxLDL remarkably of blood serum in atherosclerosis rats.3 Candesartan appeares to markedly reduce the expressions of MMP-2 and VEGF of aorta in atherosclerosis rats.更多还原