蛋白激酶C在高胆固醇血症引起内皮功能障碍中的作用

以高胆固醇饮食喂养的新西兰兔为实验对象 ,观测蛋白激酶C抑制剂 (H 7)及蛋白激酶C激动剂 (PMA) ,对乙酰胆碱 (acetylcholine,Ach)诱导的离体胸主动脉舒张反应的影响 ,及其对血栓素A2 和前列环素代谢产物生成的影响 ,探讨蛋白激酶C激活在高胆固醇血症引起的动脉内皮依赖性血管舒张功能障碍中的作用。结果显示 :H 7可显著改善高胆固醇组动脉条乙酰胆碱诱导的舒张功能障碍 ,并可显著减少有内皮高胆固醇组动脉条血栓素B2 的生成 ;PMA可显著抑制普通饮食组动脉条乙酰胆碱诱导的舒张功能 ,并可显著增加有内皮普通饮食组动脉条血栓素B2 的生成量 ;H 7及PMA对 2组动脉条 6 酮 前列腺素F1a的生成量均无显著影响。提示高胆固醇血症可激活动脉内皮蛋白激酶C ,增加内皮血管收缩性前列腺素类物质血栓素A2 的生成 ,进而引起动脉内皮依赖性舒张功能障碍。

Hypercholesterolemia Impairment of Endo-thelial Function through Protein Kinase C

In order to examine the effects of protein kinase C activation on the impaired endothelium-dependent relaxation induced by hypercholesterolemia, New Zealand white rabbits fed with cholesterol chow were used and the effects of PMA (protein kinase C activator) and H-7 (protein kinase C antagonist) on the endothelium-dependent relaxation and the vasoactive prostanoids production of thoracic aorta were evaluated in vitro. The results demonstrated that H-7 restored the impaired endothelium-dependent relaxation of aortic rings from the cholesterol group, and suppressed the abnormal release of Thromboxane B 2 from aorta with endothelium of the cholesterol group significantly. Rings from the control group treated with PMA showed decreased relaxation, and PMA significantly increased the release of Thromboxane B 2 from aortic segments with endothelium from the control group. PMA and H-7 did not cause any significant change in the production of 6-keto-Prostaglandin F 1a in either the control or cholesterol group. In conclusion, hypercholesterolemia impairs the endothelium-dependent relaxation by increasing the endothelial Thromboxane A 2 production, which is induced by the activation of protein kinase C.