肥胖大鼠血清脂联素水平与血管内皮NF-κB、VCAM-1、ICAM-1关系的研究

摘要

目的 建立肥胖大鼠模型,观察肥胖大鼠血清脂联素的变化及动脉血管内皮核因子(NF)-κB、血管内皮细胞黏附分子(VCAM)-1、细胞间黏附分子(ICAM)-1的表达,探讨其在血管病变发生发展中的作用机制.方法 4周龄雄性健康SD大鼠48只,随机分为对照组(18只)和高脂组(30只),给予高脂饲料制备肥胖大鼠模型.8周后,以高脂组大鼠的体质量超过对照组大鼠平均体质量的20%作为肥胖组大鼠.用酶联免疫法检测血清脂联素含量,应用免疫组化技术测定NF-κB、VCAM-1、ICAM-1在血管内皮的表达.结果 高脂组大鼠平均体质量明显高于对照组,(446.82 ± 10.05)g比(365.21 ± 13.20)g,P ＜ 0.01;高脂组中有22只大鼠体质量超过对照组平均体质量20%,作为实验用肥胖大鼠(肥胖组).肥胖组大鼠血清脂联素水平明显低于对照组,(0.61 ± 0.13)ng/ml比(1.00 ± 0.17)ng/ml,P ＜ 0.01,动脉血管内皮NF-κB、VCAM-1、ICAM-1阳性表达显著高于对照组,且肥胖组大鼠血清脂联素水平与血管内皮NF-κB、VCAM-1、ICAM-1表达均呈明显负相关(r ＝ -0.938 ～ -0.891,P均 ＜ 0.001).结论 高脂饮食引起的肥胖可使血清脂联素水平降低,使脂联素对NF-κB的抑制减弱,导致肥胖大鼠血管内皮VCAM-1、ICAM-1表达的增加,从而使动脉血管内膜增厚,血管结构发生改变导致血管疾病的发生.%Objective To establish an obese rat model, to observe the level of serum adiponectin and the expression of NF-κB, VCAM-1, ICAM1, to explore the mechanism of angiopathy. Methods Forty-eight four-week-old healthy male SD rats were randomly divided into control group (n = 18) and high-fat group (n = 30). The high-fat group was fed the high-fat diet to establish the obese rat model. After 8 weeks, the rats in high-fat group with body weight more than 20％ of average body weight of control group were selected as the obese rats. The level of serum adiponectin was measured by Enzyme-Linked Immuno Sorbent Assay. The expression of NF-κB, VCAM-1 and ICAM-1 in vascular endothelium was detected hy immunohistochemistry. Results The average body weight was significantly heavier in high-fat group than in control group (446.82 ± 10.05 g vs. 365.21 ± 13.20 g, P ＜ 0.01). Twenty-two rats were selected as obese rats in high-fat group (obese group) , whose body weight was 20％ more than the average weight of control group. The level of serum adiponectin were signific.antly lower in obese rats than in control group ( 0.61± 0.13 ng/ml vs. 1.00 ± 0.17 ng/ml, P ＜ 0.01). The expression of NF-κB, VCAM-1, ICAM-1 in vascular endothelial was significantly higher in ohese group than in control group. Meanwhile, the adiponectin levels were negatively correlated with NF-κB. VCAM-1. ICAM-1 in obese rats (r = -0.938 to -0.891. P ＜ 0.001). Conclusion In ohesity due to high-fat diet the level of serum adiponectin may be reduced and the inhibition of the serum adiponectin on NF-κB may he decreased, and thus the expression of VCAM-1 and ICAM-1may be increased. It causes the accumulation of artery vessel thickening and change , and causes the vascular disease.