银杏叶提取物对糖基化终末产物损伤血管内皮功能的保护作用机制研究

目的:研究银杏叶提取物(extract ofGinkgo biloba,EGb)对静脉注射外源性糖基化终末产物损伤大鼠血管内皮功能的影响及其机制。方法:按文献方法制备糖基化终末产物,大鼠尾静脉注射AGEs-BSA(100 mg/kg),每天一次,共30天,以观察AGEs-BSA对大鼠血管内皮功能的影响。同时用EGb(15或30 mg/kg)灌胃(每天一次,共30天)治疗。30天后大鼠在3%戊巴比妥麻醉下,颈动脉插管取血,检测血清一氧化氮(nitric oxide,NO)、丙二醛(malondialdehyde,MDA)、非对称性二甲基精氨酸(ADMA)的含量和超氧化物歧化酶(superoxide dismutase,SOD)、NOS及二甲基精氨酸二甲胺水解酶(DDAH)的活性。并取出胸主动脉制成3~4 mm血管环,检测乙酰胆碱诱导的内皮依赖性舒张反应及硝普钠诱导的非内皮依赖性舒张反应。结果:尾静脉注射AGEs-BSA能显著降低大鼠胸主动脉EDR反应,而对非内皮依赖性舒张反应无影响;血清NO水平及SOD活性显著降低,MDA和ADMA的浓度明显增高。EGb能剂量依赖性地保护AGEs-BSA抑制的内皮舒张功能,对AGEs-BSA所降低的血清NO水平及SOD和DDAH活性也有明显保护作用,并能减少MDA的生成。结论:EGb对AGEs-BSA所引起的血管内皮损害具有明显的保护作用,该作用可能与其抗氧化作用和保护DDAH活性、升高NO水平有关。

Protective Effects of Extract of Ginkgo biloba on Vascular Endothelial Dysfunction Induced by AGEs-BSA in Vivo

OBJECTIVE: To explore the effect of extract of Ginkgo biloba (EGb) on vascular endothelial dysfunction induced by AGEs and to investigate the potential mechanisms. METHODS: Exogenous glycosylated bovine serum Albumin (AGEs-BSA) was prepared according to the methods of article. Vascular endothelial dysfunction was induced by tail vein injection of AGEs-BSA. The treatment group rats were given tail vein injections with AGEs-BSA followed by immediate intragastric of EGb (15,30 mg/kg/day, respectively) for 30 days. At the end of 30 days period, rats were anaesthetized with an intraperitoneal injection of sodium pentobarbital. Blood samples were collected from the carotid artery for biochemical assay of NO, MDA, SOD, DDAH, ADMA. The thoracic aorta was immediately isolated and cut into rings of 3 - 4 mm. Then ACh-induced EDR response and sodium SNP-induced endothelium-independent relaxation of aortic rings were examined. RESULTS: Results from in vivo experiments showed that the injection of AGEs-BSA significantly inhibited ACh-induced EDR response, but had no effect on SNP-induced endothelial-independent relaxation. The injection of AGEs-BSA decreased concentration of serum NO, activity of serum SOD and elevated serum MDA and ADMA level. Egb markedly attenuated AGEs-BSA induced inhibition of EDR response, increase of serum MDA and ADMA level, reduction of both NO level and activity of serum SOD.