亲环素A和Krüppel样转录因子2及内皮型一氧化氮合酶在大鼠动脉粥样硬化病变过程中的表达变化

Expression changes of cyclophilin A,Krüppel-like factor 2,and endothelial nitric oxide synthase in the pathological process of atherosclerosis in rats

目的观察大鼠动脉粥样硬化病变过程中血管壁亲环素A(Cy PA)、Krüppel样转录因子2(KLF2)、内皮型一氧化氮合酶(e NOS)的表达变化。方法将雄性Wistar大鼠32只按数字表法随机分为对照组及动脉粥样硬化8、12、15周组,每组8只。给予动脉粥样硬化组高脂饲料喂养,并给予维生素D3注射液60万IU/kg一次性腹腔注射;给予对照组大鼠基础饲料喂养。在喂养第8、12、15周时处死大鼠,分离腹主动脉,行苏木素-伊红染色,免疫组化法检测动脉壁CyPA、KLF2、eNOS的表达水平。结果随着动脉粥样硬化病变进展,对照组以及动脉粥样硬化8、12、15周组大鼠分别呈现出血管正常结构、内皮细胞破坏、平滑肌细胞增生、粥样斑块形成以及钙化斑块形成等不同的特征。对照组与动脉粥样硬化8、12、15周组间血管壁CyPA、KLF2、eNOS的表达水平差异均有统计学意义(CyPA:0.0037±0.0018、0.0276±0.0090、0.0526±0.0129、0.1080±0.0388;KLF2:0.0932±0.0331、0.0415±0.0076、0.0207±0.0059、0.0014±0.0003;eNOS:0.0358±0.0185、0.0148±0.0080、0.0049±0.0025、0.0037±0.0026;F值分别为36.395、42.108、21.255,均P<0.05),且组间CyPA的表达呈增高趋势,组间两两比较差异有统计学意义(均P<0.05);KLF2表达水平呈进行性下降趋势,组间两两比较差异有统计学意义(均P<0.05);eNOS表达动脉粥样硬化12周组与15周组差异无统计学意义,其他组间差异均有统计学意义(均P<0.05)。结论伴随动脉粥样硬化病变进展,CyPA的表达进行性增高,KLF2、eNOS表达进行性下降。CyPA可能是致动脉粥样硬化病变的途径之一。

Objective To observe the expression changes of cyclophilin A （ CyPA ） , Kr＆#252;ppel-like factor 2 （KLF2）,and endothelial nitric oxide synthase （eNOS） in the pathological process of atherosclerosis in rats. Methods Thirty-two male Wistar rats were randomly divided into four groups：a control group and atherosclerosis 8,12,and 15 week groups （n=8 in each group）. The atherosclerosis groups were fed with high-fat diet,and they were given vitamin D3 600 000 IU for a single intraperitoneal injection,and the rats in the control group were fed with the basal feed. The rats were sacrificed at 8,12,and 15 weeks. Their abdominal aortas were separated and stained with hematoxylin-eosin staining. Immunohistochemical method was used to detect the expression levels of CyPA,KLF2,and eNOS on arterial walls. Results With the progression of atherosclerosis lesion,the rats in the control group,and atherosclerosis 8,12,and 15 week groups showed different characteristics, including normal vessel structure, endothelial cell damage, smooth muscle cell proliferation,formation of atherosclerotic plaque,and formation of calcified plaque. There were significantly differences in the expression levels of CyPA,KLF2,eNOS on vessel walls among the control group,atherosclerosis 8,12,and 15 week groups （CyPA：0. 0037 ＆#177; 0. 0018,0. 0276 ＆#177; 0. 0090,0. 0526 ＆#177; 0. 0129,and 0. 1080 ＆#177; 0. 0388;KLF2：0. 0932 ＆#177; 0. 0331,0. 0415 ＆#177; 0. 0076,0. 0207 ＆#177; 0. 0059, and 0. 0014 ＆#177; 0. 0003;eNOS：0. 0358 ＆#177; 0. 0185,0. 0148 ＆#177; 0. 0080,0. 0049 ＆#177; 0. 0025,0. 0037 ＆#177; 0. 0026;F=36. 395,42. 108,and 21. 255,respectively,all P〈0. 05）,and the CyPA expression showed an increasing trend among groups, and there were significant differences between the pairwise comparisons （all P〈0. 05）. The expression level of KLF2 showed a progressive declining trend,and there were significant differences between pairwise comparisons （all P 〈0. 05）;there was significant difference in eNOS expression between the atherosclerosis 12-week group and the atherosclerosis 15-week group, and there were significant differences among other groups （all P〈0. 05）. Conclusion With the progression of atherosclerotic lesions, the expression of CyPA increases progressively, and the expression levels of KLF2 and eNOS decrease progressively. This may be one of the approaches of CyPA caused atherosclerotic lesion.