慢性体外反搏对高脂饲养猪动脉内皮细胞基因表达的影响

Effect of chronic enhanced external counterpulastion on gene expression profiles of arterial endothelial cells of pigs fed with high-cholesterol diet

目的探讨慢性体外反搏对高脂饲养猪动脉内皮细胞基因表达的影响。方法选雄性乳猪22头用高脂喂养建立动脉粥样硬化模型,对模型猪进行36h体外反搏治疗。对冠状动脉作透射电镜检查。对腹主动脉作苏丹III染色,分析脂质浸润阳性率。用基因芯片分析猪的胸主动脉内皮细胞基因的表达。结果透射电镜显示,高脂组冠状动脉内皮细胞下层可见巨噬细胞和分化的泡沫细胞,正常组、高脂加反搏组内皮细胞下层完整。正常组和高脂加反搏组与高脂组腹主动脉苏丹III染色阳性率有显著差异(P<0.05)。芯片检测显示,与正常组相比,高脂组整合素β1、CTGF上调;与高脂组相比,反搏组整合素β1、CTGF,和VCAM-1下调,eNOS上调。结论慢性体外反搏可以下调动脉内皮细胞整合素β1、CTGF和VCAM-1基因的表达,降低动脉內皮细胞对脂质的摄取,改善动脉内皮功能,起到抗动脉粥样硬化的作用。

Objective To investigate the effect of chronic enhanced external counterpulastion （EECP） on gene expression profiles of arterial endothelial cells （ECs） of pigs fed with high-cholesterol diet. Methods Eight male pigs were fed with high-cholesterol diet for 12 weeks to induce arteriosclerosis and subjected to EECP for accumulative 36 h （2 h every other day for 18 sessions）. Another 8 pigs on cholesterol-enriched diet and 6 normally fed pigs served as the arteriosclerosis model group and normal control group, respectively, and the high-cholesterol diet was maintained until the end of EECP treatment. The coronary artery was then isolated for transmission electro microscopy, and the abdominal aorta was observed using Sudan III stainig. The gene expression profiles in ECs from the thoracic aorta using cDNA microarrays. Results Macrophages and foam cells were detected beneath the ECs in the coronary artery of pigs in the model group, but not in the other two groups. The ratios of Sudan Ⅲ-positive area in the celiac aorta were significantly lower in normal control and EECP groups than in the model control group （P〈0.05）. Compared with the normal control group, the gene expressions of integrins-β1 and CTGF were up-regulated in the model group. Compared with the model group, the expressions of integrins-β1, CTGF and VCAM-1 were down-regulated and eNOS up-regulated in EECP group. Conclusion Chronic EECP may reduce endothelial injury, down-regulate the gene expression level of integfin-β1, CTGF and VCAM-1, lower cholesterol uptake and attenuate arterial endothelial inflammation to protect the pigs fed with high-cholesterol diet from arteriosclerosis.