3,4,5,6-四羟基口山酮对高糖所致血管内皮依赖性舒张功能减退的保护作用

Protective effects of 3,4,5,6-tetrahydroxanthone on damages of endothelium-dependent relaxation induced by high glucose

目的:观察3,4 ,5 ,6 - 四羟基口山酮对高糖所致血管内皮依赖性舒张功能减退的保护作用。方法:在大鼠离体胸主动脉环,用高浓度葡萄糖(2 5mmol·L-1)孵育2 4h ,检测乙酰胆碱诱导的血管内皮依赖性舒张反应;人脐静脉内皮细胞株(ECV30 4 )用高浓度葡萄糖(30mmol·L-1)培养4 8h ,测定培养液中乳酸脱氢酶(LDH)活性、一氧化氮(NO)及细胞脂质过氧化物丙二醛(MDA)含量。结果:3,4 ,5 ,6 - 四羟基口山酮(1、3和10 μmol·L-1)能显著抑制高糖所致的舒血管效应减退,并且呈剂量依赖性。3,4 ,5 ,6 - 四羟基口山酮(1、3和10 μmol·L-1)能显著抑制高糖所致的内皮细胞LDH泄漏、NO释放和MDA生成的增加。结论:3,4 ,5 ,6 - 四羟基口山酮对高糖所致的血管内皮依赖性舒张功能减退有保护作用,其保护作用与抑制脂质过氧化减少血管内皮细胞损伤有关。

AIM: To investigate the protective effects of 3,4,5,6-tetrahydroxanthone on damages of endothelium-dependent relaxation induced by high glucose. METHODS: The aortic rings obtained from the rats were exposed to high glucose (25 mmol·L -1) for 24 h or endothelial cells were incubated with high glucose (30 mmol·L -1) for 48 h, respectively. Endothelium-dependent relaxation was measured. Activity of lactate dehydrogenase (LDH), contents of malondialdehyde (MDA) and nitric oxide (NO) in the medium were measured. RESULTS: Exposure of aorta rings to high glucose (25 mmol·L -1) for 24 h caused a marked decrease in endotheliun-dependent relaxation. Pretreatment with 3,4,5,6-tetrahydroxyxanthone (1, 3 or 10 μmol·L -1) or probucol (10 μmol·L -1) significantly improved endothelium-dependent relaxation in a dose-dependent manner. The release of LDH, the contents of MDA and NO in the medium marked increased after exposure of HUVEC to high glucose (30 mmol·L -1) for 48 h. Pretreatment with 3,4,5,6-tetrahydroxyxanthone (1, 3 or 10 μmol·L -1) or probucol (10 μmol·L -1) significantly decreased the increased release of LDH, the increased content of NO and MDA in the medium. CONCLUSION: 3,4,5,6-tetrahydroxanthone may preserve endothelial dysfunction induced by high glucose, and the protective effects of 3,4,5,6-tetrahydroxanthone may be related to reduction of endothelial cells damages by inhibiting lipid peroxidation.