炎症促进大鼠动脉粥样硬化初期内皮功能病变机制研究

Study on Lesion Mechanism of Primary Endothelial Function of Rats with Atherosclerosis Induced by Chronic Inflammation

目的:观察炎症因素诱导大鼠动脉粥样硬化发病过程中对血管内皮细胞的影响。方法:实验分为单纯高脂对照组和炎症组,分别腹腔注射给予无菌医用液体石蜡和酵母多糖(Zym,20mg/kg,1次/3天)。所有大鼠均喂食含3%胆固醇的高脂饲料,共8周。透射电镜观察主动脉超微结构;应用定量PCR法测定腹主动脉组织中诱导型一氧化氮合酶(iNOS)mRNA、血管细胞粘附分子(VCAM)-1 mRNA、以及基质金属蛋白酶7(MMP7)mRNA的表达。结果:炎症组可见游走于内膜下层的平滑肌细胞和和吞噬脂质颗粒的单核细胞,单纯高脂对照组仅见内皮细胞损伤和退行性变,未见内膜下层形成泡沫细胞,AS样病变较炎症组轻。与对照组相比,炎症组动脉壁iNOS mRNA表达降低,VCAM-1 mRNA及MMP7 mRNA标大量显著升高。结论:炎症刺激能够损伤动脉血管内皮细胞,诱导炎症因子释放增加,促进动脉粥样硬化的发生。

Objective： To study lesion mechanism of primary endothelial function of rats with atherosclerosis induced by chronic inflammation. Methods： Rats were randomly divided into two groups： simple high fat diet control and inflammation group, which were administrated medical grade liquid paraffin （ip）and zymosan A （Zym, 20 mg/kg, suspended in liquid paraffin, ip,once every three days） respectively. All the animals were fed with high fat diet containing 3% cholesterol for 8 weeks. At the scheduled time, rats were killed; the abdominal aortas were taken out. Ultramicrostructure was observed using transmission electron microscope. The expression of inducible nitric oxide synthase（iNOS）mRNA, vascular cell adhesion molecule （VCAM）-1 mRNA and matrix metalloproteinase（MMP）7 mRNA in aortic wall were determined with real-time quantitative PCR. Results： Only degeneration of endothelial cells could be seen in control group, but no foam cell formation in the subendothelial space. Correspondingly, there were many subendothelial smooth muscle cells and foam cells containing lipid granules in inflammation group. Compared with control group, the expression of iNOS mRNA decreased significantly in the vascular wall in inflammation group, and the expression of VCAM-1 mRNA, MMP7 mRNA increased markedly. Conclusion： Chronic inflammation can damage vascular endothelial cell, induce the release of inflammatory factors and promote the occurring of atherosclerosis.