尿毒症apoE基因敲除小鼠主动脉动脉粥样硬化的病变特征_临床医学论文.docVIP

尿毒症apoE基因敲除小鼠主动脉动脉粥样硬化的病变特征_临床医学论文 尿毒症apoE基因敲除小鼠主动脉动脉粥样硬化的病变特征_临床医学论文 作者：申燕，袁祖贻，肖嫣，吴岳，赵燕，田雨灵，王丽君，梁萧 【摘要】 目的 观察尿毒症apoE-/-小鼠主动脉粥样硬化(As)病变特征及MMP的表达。方法 以apoE-/-小鼠为研究对象，通过2步外科手术法建立尿毒症模型，对照组行假手术。造模后检测肾功能，判断造模是否成功。造模后10周，检测血清MMP浓度;主动脉根部切片油红O染色计算斑块相对面积，天狼星红染色计算斑块内胶原含量，α肌动蛋白、MAC3免疫组化染色检测斑块内SMC及巨噬细胞的含量;RT法检测主动脉MMP的表达。结果 造模后肾功能检测显示造模成功。尿毒症组与对照组相比：主动脉根部As斑块相对面积提高、斑块内胶原含量减少、SMC成分减少、巨噬细胞含量增加，血清MMP浓度及主动脉MMP的表达提高。结论 尿毒症apoE-/-小鼠主动脉加速发展的As伴随着斑块的稳定性降低。 【关键词】 尿毒症;apoE-/-小鼠;动脉粥样硬化;MMP 　　Cardiovasology, Beijing Xishan Hospital, Beijing 100144, China)ABSTRACT: Objective To observe the features of aortic atherosclerosis (As) and the expression of MMP control mice were shamoperated. After uremia was induced, renal function was detected to evaluate the success of the model construction. Ten weeks after uremia induction, serum MMP9 concentration was determined; frozen sections of aortic root were examined for the lesion features of As: relative area by oil red O stain, collagen content by sirius red stain, SMC content and macrophage infiltration in the plaque by αactin and Mac3 immunohistochemistry staining, respectively. The expression of aortic MMP9 mRNA was determined by RTPCR. Results After induction of uremia, renal function indicated that the model was successfully constructed. The relative area of aortic root plaque, the degree of macrophage infiltration in plaque, serum MMP9 concentration and the expression of MMP9 mRNA in aorta all increased. Meanwhile, collagen and SMC content in plaque decreased in uremia group compared with that in control group. Conclusion The accelerated atherogenesis in uremic apoE-/- mice is accompanied with the instability of the plaque. 　　KEY WORDS: uremia; apoE-/- mice; atherosclerosis; MMP 　　慢性肾功能衰竭(chronic renal failure, CRF)患者50%以上的死亡率是由心血管疾病引起[1]。在慢性肾脏病患者开始透析前，冠心病的患病率接近53%[2]，死于心血管事件的危险性是普通人群的20倍[3]。CRF患者冠心病的高发病率已被回顾性以及更具有说服力的前瞻性研究所证实[4]。心血管疾病的治疗有长足的进展。但是，CRF患者仍然有高的动脉粥样硬化(atherosclerosis, As)疾病发病率和死亡率。本研究拟在前期研究建立尿毒症性As动物模型(尿毒症apoE-/-小鼠)的基础上，进一步