Kim J, Li Qun, Fang Cindy X, Ren J
Center for Cardiovascular Research and Alternative Medicine, Division of Pharmaceutical Sciences, University of Wyoming, Laramie, WY 82071, USA.
Acta Pharmacol Sin. 2006 May;27(5):536-42. doi: 10.1111/j.1745-7254.2006.00320.x.
Ginkgo biloba extract is a natural product used widely for cerebral and cardiovascular diseases. It is mainly composed of terpene lactones (ginkgolide A and B) and flavone glycosides (eg quercetin and kaempferol). To better understand the cardiac electromechanical action of Ginkgo biloba extract in normal and diabetic states, this study was designed to examine the effect of ginkgolide B on cardiomyocyte contractile function under normal and high-glucose environments.
Isolated adult rat ventricular myocytes were cultured for 6 h in a serum-free medium containing either normal (NG; 5.5 mmol/L) or high (HG; 25.5 mmol/L) glucose with or without ginkgolide B (0.5-2.0 microg/mL). Mechanical properties were evaluated using the IonOptix MyoCam system. Contractile properties analyzed included peak shortening (PS), maximal velocity of shortening/relengthening (+/-dl/dt), time-to-PS (TPS) and time-to-90% relengthening (TR90). Levels of essential Ca(2+) regulatory proteins sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a), phospholamban (PLB) and Na(+)-Ca(2+) exchanger (NCX) were assessed by Western blotting.
Ginkgolide B nullified HG-induced prolongation in TR90. However, ginkgolide B depressed PS, +/-dl/dt and shortened TPS in NG and HG cells. Ginkgolide B also prolonged TR90 in NG cells. Western blot analysis revealed that HG upregulated SERCA2a and downregulated PLB expression without affecting that of NCX. Ginkgolide B disrupted the NG-HG response pattern in SERCA2a and NCX without affecting that of PLB.
Ginkgolide B affects cardiomyocyte contractile function under NG or HG environments in a paradoxical manner, which may be attributed to uneven action on Ca(2+) regulatory proteins under NG and HG conditions.
银杏叶提取物是一种广泛用于治疗脑和心血管疾病的天然产物。它主要由萜类内酯（银杏内酯A和B）和黄酮苷（如槲皮素和山奈酚）组成。为了更好地了解银杏叶提取物在正常和糖尿病状态下对心脏机电活动的影响，本研究旨在检测银杏内酯B在正常和高糖环境下对心肌细胞收缩功能的作用。
将分离的成年大鼠心室肌细胞在含有正常（NG；5.5 mmol/L）或高糖（HG；25.5 mmol/L）的无血清培养基中培养6小时，培养基中添加或不添加银杏内酯B（0.5 - 2.0μg/mL）。使用IonOptix MyoCam系统评估机械性能。分析的收缩性能包括峰值缩短（PS）、最大缩短/再延长速度（+/-dl/dt）、达到PS的时间（TPS）和达到90%再延长的时间（TR90）。通过蛋白质免疫印迹法评估内质网钙ATP酶（SERCA2a）、受磷蛋白（PLB）和钠钙交换体（NCX）等必需钙调节蛋白的水平。
银杏内酯B消除了HG诱导的TR90延长。然而，银杏内酯B降低了NG和HG细胞中的PS、+/-dl/dt并缩短了TPS。银杏内酯B还延长了NG细胞中的TR90。蛋白质免疫印迹分析显示，HG上调了SERCA2a并下调了PLB表达，而不影响NCX的表达。银杏内酯B破坏了NG - HG条件下SERCA2a和NCX的反应模式，但不影响PLB的反应模式。
银杏内酯B在NG或HG环境下以矛盾的方式影响心肌细胞收缩功能，这可能归因于在NG和HG条件下对钙调节蛋白的作用不均衡。
