摘要
目的探讨使用增强型体外反搏器(EECP)提高血流剪切应力对高胆固醇血症实验猪血管病理形态、血管内皮形态与功能及核因子κB(NFκB)表达的影响。方法健康雄性家猪随机分为普通饲料组、高脂对照组、高脂反搏组。后两组同量持续高胆固醇饲料喂养建立高胆固醇血症及早期动脉粥样硬化动物模型。高脂反搏组在高胆固醇喂养2个月后进行体外反搏。15周后取出冠状动脉、胸主动脉和腹主动脉行病理形态学观察和NFκB免疫荧光激光共聚焦扫描。结果高脂对照组及高脂反搏组血脂水平较普通饲料组显著升高(P<0.01),而高脂对照组与高脂反搏组之间血脂水平差异无统计学意义(P>0.05)。主动脉大体苏丹Ⅲ染色示高胆固醇血症猪斑块形成较普通饲料组增多;而高脂反搏组斑块/内膜面积比[(3.33±2.40)%]显著少于高脂对照组[(12.03±7.12)%](P<0.05)。扫描电镜示高脂对照组内皮细胞排列紊乱,大量破坏脱落,有较多血小板黏附;高脂反搏组内皮细胞较完整,沿血流方向梭形排列,血小板黏附较少。透射电镜示高脂对照组内皮细胞变性凋亡脱落显著,内皮下大量泡沫细胞积聚,平滑肌细胞呈合成型改变,大量增生并向内膜移行;而高脂反搏组上述改变明显减轻。冠状动脉HE染色及弹力纤维染色示高脂对照组弹力纤维紊乱断裂,内膜较普通饲料组增厚[(24.36±9.72)μm比(9.97±4.02)μm,P<0.05];而高脂反搏组的内膜增厚比高脂对照组明显减少[(11.87±5.95)μm比(24.36±9.72)μm;P<0.05]。免疫荧光激光共聚焦扫描示高胆固醇血症猪冠脉内皮细胞及平滑肌细胞的细胞核NFκB荧光强度较普通饲料组增高,但高脂反搏组荧光强度较高脂对照组减少(P<0.05)。结论通过体外反搏提高血流剪切应力可改善血管内皮细胞形态与功能,减轻内膜增生和血管重塑,从而抑制高胆固醇血症猪早期动脉粥样硬化的形成和进展。其机制可能与下调NFκB的活性表达有关。
Objective To study the effects of enhanced external counterpulsation （EECP） on the vascular morphology, and endothelial function using experimentally induced hypercholesterolemic pigs. Methods Thirty five male pigs were randomly divided into three groups： 7 normal control animals, 11 hypercholesterelemic animals, and 17 hypercholesterolemic animals receiving EECP. Serum cholesterol was measured. The coronary arteries and aortas were sampled for histopathologic and ultrastructural examination. The NF-κB protein expression of porcine coronary arteries was investigated by immunofluorescence. Results Compared with the normal controls, serum cholesterol levels were significantly higher in the hypcrcholesterolemic animals with or without EECP. The plaque/intimal area ratio of the aorta decreased significantly in animals receiving EECP [ （ 3.33 ± 2.40 ） %, versus （ 12. 03 ± 7. 12 ） % in those without EECP, P 〈0. 05]. Lipid deposition, endothelial damage and proliferation of smooth muscle cells were less severe in animals receiving EECP than those not. Moreover, activation and expression of NF-κB also decreased significantly （ P 〈 0. 05 ） in animals receiving EECP. Conclusions EECP improves the morphology and function of vascular endothelium, and retards the development and progression of atherosclerosis, likely through the inhibition of NF-κB signaling pathway.
出处
《中华病理学杂志》
CAS
CSCD
北大核心
2006年第3期159-164,共6页
Chinese Journal of Pathology
基金
国家自然科学基金资助项目(501134103048)
国家"十.五"科技攻关计划资助项目(2001BA706B07)
广东省科技计划项目(2003C30601)
关键词
动脉硬化
内皮
血管
猪
应力
物理
反搏动术
Arteriosclerosis
Endothelium, vascular
Swine
Stress, mechanical
Counterpulsation
