葛根素对糖基化终产物损伤血管内皮功能的保护作用

Protection of Puerarin on Impaired Vascular Endothelial Function Induced by Glycosylated Protein

目的探讨葛根素对糖基化牛血清白蛋白（glycosylatedbovineserumalbumin，GBSA）损伤兔血管内皮依赖性舒张功能的影响及机制。方法糖基化牛血清白蛋白孵育兔离体胸主动脉环30min诱导血管内皮功能损伤，观察葛根素（0．25、0．5和1g·L-1）对糖基化牛血清白蛋白诱导血管内皮功能损伤的保护作用，以及N-硝基-L-精氨酸（30μmol·L-1）和吲哚关辛（10μμ1xmol·L-1）对葛根素保护作用的影响，并检测血管组织中一氧化氮（nitricoxide，NO）和丙二醛（malonaldehyde，MDA）含量及超氧化物歧化酶（superoxidedismutase，SOD）的活性。结果200mg·L“糖基化牛血清白蛋白孵育血管环30min，明显降低乙酰胆碱诱导的内皮依赖性舒张反应，没有影响硝普钠诱导的非内皮依赖性舒张反应，血管组织中-氧化氮含量和超氧化物歧化酶活性降低而丙二醛含量增加。用0．25～1g·L-1葛根素分别孵育血管环15min，再与200mg·L-1糖基化牛血清白蛋白共同孵育30min，明显改善糖基化牛血清白蛋白所致的血管舒张功能的损害，升高血管组织中-氧化氮含量和超氧化物歧化酶活性而降低丙二醛含量。N-硝基-L、精氨酸部分地抑制了葛根素（1g·L-1）对血管内皮功能的保护作用，而吲哚关辛没有影响葛根素（1g·L-1）的保护效应。结论葛根素具有对抗糖基化牛血清白蛋白损伤血管内皮依赖性舒张的作用，其机制可能与增加-氧化氮合成及抗氧化有关。

OBJECTIVE To investigate the effects of puerarin on impaired endothelium-dependent relaxation induced by glycosy- lated bovine serum albumin （GBSA） in rabbit thoracic aorta and its mechanisms. METHODS The rings were incubated with GBSA for 30 min to induce endothelial dysfunction, and with puerafin（0. 25,0. 5 and 1 g .L -1 ） , N-nitro-L-arginine methyl ester （L-NAME, 30μ mol .L-1） , and indomethacin（ 10 μ mol. L- 1 ） to investigate the protective effect of puerarin on impaired vascular endothelial function elicited by GBSA, and the effect of L-NAME and indomethacin on the protective effect of puerarin. Moreover, the content of nitric oxide（NO） and malonaldehyde（MDA） and the activity of superoxide dismutase（SOD） in the rings were measured. RESULTS Exposure of aortic rings to GBSA（ 200 mg. L-1） for 30 rain resulted in a significant inhibition of endothelium-dependent relaxation, but had no affect on endothelium-independent relaxation. GBSA significantly decreased the level of NO and the activity of SOD but largely increased the content of MDA in vascular tissues. Pre-incubation of aortic rings with puerarin markedly attenuated the inhibition of endothelium-dependent relaxation induced by GBSA. This protective effect of puerarin （ 1 g ~ L-1 ） was partially inhibited by L- NAME but not by indomethacin. Puerarin obviously increased NO level and SOD activity but evidently decreased MDA content in rings. CONCLUSION Puerarin can protect against vascular endothelial dysfunction caused by GBSA and its mechanisms may be re- lated to enhancing NO synthesis and its anti-oxidation.