【作者】 王春燕；

【导师】 武宇明；

【作者基本信息】 河北医科大学 ， 生理学， 2008， 硕士

【摘要】 银杏叶提取物(ginkgo biloba extract, GBE)是从银杏中提取的天然化合物,主要包括6%的萜内酯和24%的黄酮。银杏苦内酯B(ginkgolide B)是萜内酯类的一种主要活性物质。大量研究发现银杏苦内酯B为血小板活化因子的天然拮抗剂,并已在较大范围内展现出生物学活性。银杏苦内酯B可通过调节血流量、降低缺血再灌注损伤和抑制血小板凝集等药理作用,对心脑血管产生保护功效。银杏苦内酯B可引起血管舒张,但其作用机制尚不明确。有研究显示银杏苦内酯B可浓度依赖性的抑制L-型钙电流和部分减轻缺血再灌注过程中的钙超载。通过使用全细胞膜片钳技术证明了在心室肌细胞上银杏苦内酯B可浓度依赖性的缩短动作电位时程,主要与增大延迟整流型钾电流有关。由于压力感受器活动和反射在维持血压稳定方面起重要作用,而银杏苦内酯B对它们的影响至今无报道。因此本课题对以上两部分进行了研究:1银杏苦内酯B对麻醉大鼠颈动脉窦压力感受性反射的作用目的:旨在观察银杏苦内酯B对麻醉大鼠颈动脉窦压力感受性反射的作用。方法:采用本实验室自行设计的实验程序,隔离灌流30只麻醉雄性大鼠的颈动脉窦区,同时记录动脉血压的变化,并绘制压力感受性反射的功能曲线。结果:(1)银杏苦内酯B (ginkgolide B 0.1, 1, 10μmol/L)可以剂量依赖性的抑制大鼠颈动脉窦压力感受性反射,引起压力感受性反射的功能曲线向右上方移动,曲线斜率明显减小,血压反射性下降的幅度减小。曲线最大斜率(peak slop, PS)由对照时的0.46±0.01分别降至0.37±0.01,0.32±0.01,0.23±0.01。反射性血压下降幅度(reflex decrease, RD)由对照时的(46.50±1.38) mmHg分别降至(40.00±0.89),(34.83±1.94),(28.33±1.50) mmHg。阈压(threshold pressure, TP)由(65.46±1.76) mmHg分别增至(71.66±0.84),(75.18±1.56),(84.56±1.76) mmHg;平衡压(equilibrium pressure, EP)由(93.94±0.82) mmHg分别增至(96.28±1.10),(98.29±0.90),(100.64±1.01) mmHg ;饱和压(saturation pressure, SP)由(186.33±2.73) mmHg分别增至(192.00±2.37),(195.83±2.04),(205.17±2.14) mmHg。(2)预先应用钙通道的开放剂Bay K8644 (500 nmol/L),可以完全取消银杏苦内酯B的抑制作用。(3)预先应用钾通道的阻断剂四乙胺(tetraethylammonium, TEA, 1 mmol/L),银杏苦内酯B的上述作用也被完全取消。结论:银杏苦内酯B对大鼠颈动脉窦压力感受性反射有抑制作用,此作用与银杏苦内酯B减少颈动脉窦压力感受器神经末梢钙离子内流和增加钾离子外流有关。2银杏苦内酯B对麻醉大鼠颈动脉窦压力感受器活动的作用目的:本文旨在观察银杏苦内酯B对大鼠颈动脉窦压力感受器活动的影响。方法:采用本实验室自行设计的实验程序及记录方法,隔离灌流30只麻醉雄性大鼠颈动脉窦区,记录窦神经放电,并绘制压力感受器活动的机能曲线。结果:(1)银杏苦内酯B (ginkgolide B 0.1, 1, 10μmol/L)可以剂量依赖性的抑制大鼠颈动脉窦压力感受器的活动,引起压力感受器活动的机能曲线向右下方移动,曲线最大斜率明显减小,窦神经放电的最大积分值显著下降。曲线最大斜率(peak slop, PS)由对照时的(3.08±0.11) %mmHg-1,分别降至(2.52±0.06),(2.22±0.05),(2.00±0.07) %mmHg-1。最大积分值(PIV)由(331.17±3.76) %分别降至(273.67±4.03), (243.67±3.72),(213.67±5.16) %;阈压(threshold pressure, TP)由(44.16±1.50) mmHg分别增至(51.81±1.28),(58.67±3.02),(63.42±1.44) mmHg;饱和压(saturation pressure, SP)由(161.33±2.07) mmHg分别增至(172.33±1.03),(181.33±2.16),(188.17±1.17) mmHg。(2)预先应用钙通道的开放剂Bay K8644 (500 nmol/L),可以完全取消银杏苦内酯B的抑制作用。( 3 )预先应用钾通道的阻断剂四乙胺(tetraethylammonium, TEA, 1 mmol/L),银杏苦内酯B的上述作用也被完全取消。结论:银杏苦内酯B对大鼠颈动脉窦压力感受器活动有抑制作用,此作用与银杏苦内酯B减少颈动脉窦压力感受器神经末梢钙离子内流和增加钾离子外流有关。更多还原

【Abstract】 Ginkgo biloba extract (GBE) is a natural compound derived from the Ginkgo biloba and mainly composed of 6% terpene lactones and 24% flavonol glycosides. Ginkgolide B is a major active component of terpene lactones. Numerous studies have showed ginkgolide B, a potent antagonist of platelet-activating factor, exhibits a wide range of biological effects. Ginkgolide B has been used for cardiovascular and cerebrovascular disease by improving blood flow, reducing ischemia-reperfusion injury or inhibiting platelets. Ginkgolide B produces vasorelaxation, but the mechanism of ginkgolide B on vascular smooth muscles function is still essentially unknown. Some other experiments have already demonstrated that ginkgolide B decreases L-type calcium current (ICa,L) in a concentration-dependent manner and partially inhibits calcium overload during ischemia. Ginkgolide B may shorten the action potential duration in a concentration-dependent manner which mainly due to the increase of the delayed rectifier potassium current (Ik) in single ventricular myocytes by using patch-clamp techniques. It is well known that baroreflex is a major way to modulate blood pressure. The effects of ginkgolide B on carotid sinus baroreceptor activity and baroreflex have not been reported yet; the goals of the present research were to observe these effects of ginkgolide B.1 Effects of ginkgolide B on carotid sinus baroreflex in anesthetized male ratsObjective: To study the effects of ginkgolide B on carotid sinus baroreflex (CSB).Methods: The functional curve of carotid sinus baroreflex was measured by recording the changes of arterial pressure in 30 anesthetized male rats with isolated perfusing carotid sinus.Results: (1) ginkgolide B (0.1, 1, 10μmol/L) inhibited CSB, which shifted the functional curve of the baroreflex to the right and upward, with a marked decrease in peak slope (PS) and reflex decrease (RD) in blood pressure in a concentration-dependent manner. PS decreased from 0.46±0.01 to 0.37±0.01, 0.32±0.01, 0.23±0.01 respectively. RD decreased from (46.50±1.38) mmHg to (40.00±0.89), (34.83±1.94), (28.33±1.50) mmHg; threshold pressure (TP) increased from (65.46±1.76) mmHg to (71.66±0.84), (75.18±1.56), (84.56±1.76) mmHg; equilibrium pressure (EP) increased from (93.94±0.82) mmHg to (96.28±1.10), (98.29±0.90), (100.64±1.01) mmHg; saturation pressure (SP) increased from (186.33±2.73) mmHg to (192.00±2.37), (195.83±2.04), (205.17±2.14) mmHg respectively. (2) Pretreatment with Bay K8644 (500 nmol/L), an agonist of L-type calcium channel, completely eliminated the effects of ginkgolide B (1μmol/L) on the CSB. (3) Pretreatment with tetraethylammonium (TEA, 1 mmol/L), an inhibitor of potassium current, completely abolished the above effects of ginkgolide B (1μmol/L) on CSB.Conclusion: Ginkgolide B inhibits the CSB in anesthetized male rats, which is mediated by decreased calcium influx and increased potassium efflux in baroreceptor nerve ending.2 Effects of ginkgolide B on carotid sinus baroreceptor activity in anesthetized male ratsObjective: To study the effects of ginkgolide B on carotid baroreceptor activity (CBA).Methods: The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid baroreceptor were measured by recording sinus nerve afferent discharge in 30 anesthetized male rats with perfused isolated carotid sinus.Results: (1) ginkgolide B (0.1, 1, 10μmol/L) inhibits CBA, which shifted FCCB to the right and downward. There was a marked decrease in peak slope (PS) and peak integral value (PIV) of carotid sinus nerve charge in a concentration-dependent manner. PS decreased from (3.08±0.11) %mmHg-1 to (2.52±0.06), (2.22±0.05), (2.00±0.07) %mmHg-1, respectively. PIV decreased from (331.17±3.76) % to (273.67±4.03), (243.67±3.72), (213.67±5.16) %, respectively; threshold pressure (TP) increased from (44.16±1.50) mmHg to (51.81±1.28), (58.67±3.02), (63.42±1.44) mmHg; saturation pressure (SP) increased from (161.33±2.07) mmHg to (172.33±1.03), (181.33±2.16), (188.17±1.17) mmHg. (2) Pretreatment with Bay K8644 (500 nmol/L), an agonist of L-type calcium channel, completely eliminated the effects of ginkgolide B (1μmol/L) on CBA. (3) Pretreatment with tetraethylammonium (TEA, 1 mmol/L), an inhibitor of potassium current, completely abolished the above effects of ginkgolide B (1μmol/L) on CBA.Conclusion: Ginkgolide B inhibits CBA in anesthetized male rats, which is mediated by decreased calcium influx and increased potassium efflux in baroreceptor nerve ending.更多还原