银杏内酯B对实验性糖尿病血管病变的保护作用

目的:探讨银杏内酯B对实验性糖尿病大鼠血管张力的作用及其可能机制。方法:雄性S-D大鼠24只,随机分成正常对照组(normal control group,NC group)、银杏内酯B组(Ginkgolide B group,GB group)、糖尿病模型组(diabetes melites group,DM group)、糖尿病模型+银杏内酯B(diabetes melites+Ginkgolide B group,DM+GBgroup)处理组。采用腹腔注射链脲佐菌素(Streptozocin,STZ)的方法建立糖尿病模型;银杏内酯B干预8周后,采用离体血管灌流的方法,测定各组大鼠胸主动脉环对乙酰胆碱(acetylcholine,ACh)诱导的内皮依赖性血管舒张反应,运用非特异性NOS抑制剂L-NAME与cGMP抑制剂亚甲蓝预孵育血管环20min后,观察其对去氧肾上腺素(Pheny-lephrine,PE)的收缩张力变化;同时检测各组大鼠血浆血小板活化因子(Platelet-Activating Factor,PAF)水平及胸主动脉环匀浆NO含量、NOS活性。结果:与NC组相比,DM组大鼠胸主动脉环对ACh诱导的血管舒张反应明显降低(P<0.01);与DM组相比,DM+GB组胸主动脉环对ACh诱导的舒张反应明显改善(P<0.05),与NC组相类似(P>0.05);而GB组与NC组相比其差异亦无统计学意义(P>0.05);NC组主动脉血管环分别经L-NAME和亚甲蓝预孵育后,与孵育前相比,其对PE诱导的收缩幅度明显增强(P<0.01);但在DM组中,抑制剂孵育前、后主动脉环对PE诱导的收缩幅度其差异无统计学意义(P>0.05);而在DM+GB组大鼠中,抑制剂孵育后主动脉环对PE诱导的收缩幅度高于孵育前(P<0.05),但GB组中抑制剂孵育前或孵育后主动脉环对PE诱导的收缩幅度分别与NC组相应的指标相比无统计学差异(P>0.05)。生化检查显示,与NC组相比,DM组血浆PAF水平增高,胸主动脉环NOS活性及NO含量降低(P<0.01);同DM组相比,DM+GB组大鼠血浆PAF水平降低(P<0.01),胸主动脉NOS活性及NO水平明显改善(P<0.01)。结论:GB具有降低PAF水平,从而改善实验性糖尿病大鼠血管张力的作用,其机制可能通过NOS-GC-NO途径而实现的,但其确切机制有待进一步的深入研究。

Effects of Ginkgolide B on Experimental Diabetic Angiopathies Protective Effect and Its Mechanism

Objective:To explore the effects of ginkgolide B on vascular tension and its possible mechanism using diabetic model of rats.Methods:24 male S-D rats were divided randomly into four groups,including normal control group(NC group),ginkgolide B group(GB group),diabetes group(DM group) and diabetic model + ginkgolide B(DM+GB group) group.The model of diabetes is established by intraperitoneal injection of streptozotocin(STZ,65mg/kg).After 8 weeks with ginkgolide B intervention,the tension of the thoracic aortic ring(TAR) in each group of rats was measured by using blood vascular perfusion in vitro,which was induced by acetylcholine(ACh);their changes of contract tension to phenylephrine(PE) were also observed after pretreatment with L-NAME(non-specific NOS inhibitor) and methylene blue(cGMP inhibitor) for 20 minutes.The levels of platelet-activating factor(PAF) in plasma,nitric oxide(NO) from TARs were also detected,as well as the activity of NOS from TARs.Results:Compared with NC group,ACh-induced vasodilation of TAR in DM group was lower(P<0.01);whereas ACh-induced relaxation of TAR in DM+GB Group was significantly improved(P<0.05),compared with DM group,and similar to that in NC group;the difference of ACh-induced vasodilation between GB group and NC group was not statistically significant(P>0.05).After pre-incubated L-NAME and methylene blue,the contraction amplitudes of TAR induced by PE were significantly increased(P<0.01),compared to that before treatment with the inhibitors in NC group,and similar to that observed in DM+GB group(P<0.05);there were no significant differences(P>0.05) before or after pretreatment with the inhibitors in DM group.Whereas the differences of contraction amplitudes of TARs between before or after incubation in GB group Corresponding NC group were not existed significantly(P>0.05).Biochemical detections showed:compared with that in NC group,the level of PAF in plasma was increased,whereas the level of NO and the activity of NOS from TARs were decreased in DM group(P<0.01).However,compared with that in DM group,the level of PAF in plasma was decreased(P<0.01) in DM+ GB group,whereas the level of NO and the activity of NOS from TARs were significantly risen(P<0.01).Conclusion:GB can improve Ach-induced endothelium-dependent relaxation of TARs in the diabetic model of rat through reducing PAF levels,the mechanism might be executed by NOS-GC-cGMP pathway,but the accurate pathway need to research in depth.