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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。
Objective To investigate the effect of κ-opioid receptor (κ-OR) selective agonist U50,488H on vascular endothelial function in hyperlipidemic rats and its mechanism. Methods Adult SD rats were fed with normal and high-fat diet for 14 weeks, intraperitoneal injection of U50, 488H and κ-OR blocker nor-BNI every other day, blood was collected from inferior vena cava after anesthesia, total cholesterol (TC) and low density Lipoprotein (LDL) levels. Transmission electron microscopy was used to observe ultrastructural changes of arterial endothelial cells and smooth muscle cells. To observe the relaxation of the thoracic aorta to the endothelium-dependent vasodilator acetylcholine (ACh) and endothelium-independent vasodilator (SNAP). Results High-fat diets could significantly increase serum TC and LDL in rats, and markedly decrease endothelium-dependent vasodilation in aorta. The ultrastructure of arterial endothelial cells and smooth muscle cells were observed under transmission electron microscope. U50,488H can significantly reduce endothelium-dependent vasodilatation dysfunction caused by hyperlipidemia and ultrastructure damage of arterial endothelial cells and smooth muscle cells, and the effect of U50,488H can be blocked by nor-BNI. Conclusion There is endothelial dysfunction in hyperlipidemic rats. U50,488H can improve endothelial dysfunction and dysfunction induced by hyperlipidemia by activating κ-OR.