U50,488H对高脂大鼠血管内皮功能的影响

目的 探讨κ-阿片受体（κ-OR）选择性激动剂U50,488H对高脂大鼠血管内皮功能的影响及其机制。方法 成年SD大鼠分别饲以正常和高脂饲料14周，腹腔隔日注射U50,488H和κ-OR阻断剂nor-BNI，麻醉后下腔静脉取血，检测总胆固醇（TC）及低密度脂蛋白（LDL）的水平。透射电子显微镜观察动脉内皮细胞和平滑肌细胞的超微结构改变。观察胸主动脉对内皮依赖性血管舒张剂乙酰胆碱（ACh）及内皮非依赖性血管舒张剂（SNAP）的舒张反应。结果 高脂饲料喂养可引起大鼠血清TC和LDL显著升高；主动脉血管内皮依赖性舒张功能显著降低。透射电镜下可见动脉内皮细胞和平滑肌细胞的超微结构出现损伤。U50,488H可显著减轻高脂血症引起的血管内皮依赖性舒张功能障碍和动脉内皮细胞与平滑肌细胞超微结构损伤，κ-OR阻断剂nor-BNI可以阻断U50,488H的上述作用。结论 高脂血症大鼠存在内皮功能障碍，U50,488H可通过激活κ-OR改善高脂血症导致的内皮结构改变和功能障碍。

Effect of U50,488H on vascular endothelial function in rats with hyperlipidemia

AIM To study the effect of U50,488H, a selective agonist of kappa-opioid receptor, on vascular endothelial functions in rats with hyperlipidemia. METHODS Adult SD rats were fed with normal or high-fat diet for 14 weeks, respectively. U50,488H and normal saline (NS) were intraperitoneally injected on alternate days. Blood samples were harvested from inferior vena cava after anesthesia and total cholesterol and low-density lipoprotein were then detected. Ultrastructural changes of artery endothelial cells and smooth muscle cells were observed with transmission electron microscopy (TEM). The aorta was separated to observe the vasorelaxation reaction of thoracic aorta in response to acetylcholine (ACh), an endothelium-dependent vasodilating agent and SNAP, an endothelial-independent vasodilatation agent. RESULTS Endothelial structures were impaired under electron microscope in rats fed with a high-fat diet. There was a significant rise in blood lipid levels and a significantly lower thoracic aorta response to ACh. With treatment of U50,488H, endothelial structure and functions were significantly improved compared with those in high-fat diet group. The effects of U50,488H were blocked by nor-BNI, a selective kappa-opioid receptor antagonist. CONCLUSION Kappa-opioid receptor stimulation with U50,488H improves endothelial structure and functions in rats with hyperlipidemia.