银杏叶提取物对离体大鼠颈上神经节烟碱传递的影响
|
摘要
目的：研究银杏叶提取物（EGb761）对离体大鼠颈上神经节烟碱传递过程的影响。方法：应用细胞内生物电记录技术。结果：EGb761在10-6～10-1g/L的浓度灌流神经节1～10分钟，可逆性的部分或完全抑制42个实验细胞的快兴奋性突触后电位（f-EPSP），其中38个细胞不伴有膜电位的改变，4个细胞伴有膜的缓慢除极化，膜电位恢复到原水平时，抑制作用仍然存在；10-6～10-1g/L的EGb761单独灌流24个细胞1～10分钟，21个细胞的膜电位无变化，2个细胞轻度除极化和1个细胞发生先超极化后除极化的双向反应；2.0～3.5×10-1g/L的EGb761灌流（n=10）使细胞膜发生除极化（n=7），无变化（n=2）和超级化（n=1）的反应；膜电阻均无可测性改变；10-1g/L的EGb761不影响乙酰胆碱（Ach）和氨甲酰胆碱（Carb）引起的膜除极化反应。结论：10-6～10-1g/L的EGb761对离体大鼠颈上神经节突触烟碱传递的抑制作用与突触前机制有关，可能抑制了突触前膜的钙离子内流，从而减少了Ach递质的释放，使f-EPSP的幅度减小甚至消失
Object: To study the effects of EGb761 on nicotinic transmission in the isolated superior ganglia of the Wistar rats. Method: Intracellular recording technique. Results: At the concentractions of 10-6~10-1g/L for 1~10minutes, EGb761 can reduced or cancelled the amplitude of the fast excitarory postsynaptic potential(f-EPSP) induced by the single stimulation of the preganglionic sympathetic trunk (n=42),with the memberane potentials of 38 cells unchanged and the memberane of 4 cells depolarized moderately; When the memberane potentials return to the base line,the inhibition effects of EGb761 on f-EPSP still existed.During the 1~10 minutes of perfusion with EGb761(10-6~10-1g/L, n=24),the memberane potentials of 21 cells weren't alerted,two cells has slight depolarization,and one depolarized after hypolarized. When perfused with EGb761(2.0~3.5×10-1g/L,n=10), 7 cells depolarized moderately,2 cells unchanged, and one hypolarized. The memberane resistance were not significantly alerted at both concentrations. EGb761 have no effects on the depolarization by exogenous acetycholine(Ach) and carbachol(Carb). EGb761(10-1g/L) antagonized the facilitation of high Ca2+(5mmol/L) Kerb's solution on the f-EPSP, and enhanced the depressant effect of low Ca2+ Kerb's solution.Conclusion:EGb761 can inhibited reversedly the nicotinic transmission at superior cervical ganglia probably by presynaptic mechanism, relating to the inhibition of the Ca2+ influx
Object: To study the effects of EGb761 on nicotinic transmission in the isolated superior ganglia of the Wistar rats. Method: Intracellular recording technique. Results: At the concentractions of 10-6~10-1g/L for 1~10minutes, EGb761 can reduced or cancelled the amplitude of the fast excitarory postsynaptic potential(f-EPSP) induced by the single stimulation of the preganglionic sympathetic trunk (n=42),with the memberane potentials of 38 cells unchanged and the memberane of 4 cells depolarized moderately; When the memberane potentials return to the base line,the inhibition effects of EGb761 on f-EPSP still existed.During the 1~10 minutes of perfusion with EGb761(10-6~10-1g/L, n=24),the memberane potentials of 21 cells weren't alerted,two cells has slight depolarization,and one depolarized after hypolarized. When perfused with EGb761(2.0~3.5×10-1g/L,n=10), 7 cells depolarized moderately,2 cells unchanged, and one hypolarized. The memberane resistance were not significantly alerted at both concentrations. EGb761 have no effects on the depolarization by exogenous acetycholine(Ach) and carbachol(Carb). EGb761(10-1g/L) antagonized the facilitation of high Ca2+(5mmol/L) Kerb's solution on the f-EPSP, and enhanced the depressant effect of low Ca2+ Kerb's solution.Conclusion:EGb761 can inhibited reversedly the nicotinic transmission at superior cervical ganglia probably by presynaptic mechanism, relating to the inhibition of the Ca2+ influx
引文
1. Nathan P. Can the cognitive enhancing effects of ginkgo biloba be explained by its pharmacology[J]? Med Hypotheses,2000 Dec;55(6):491-3.
2. Lagente V, Boichot E, Carre C,et al. Effects of the platelet activating factor ant- agonists BN 52021 and BN 50730 on antigen-induced bronchial hyperresponsiveness and eosinophil infiltration in lung from sensitized guinea-pigs[J]. Clin Exp Allergy, 1993 Dec;23(12):1002-10.
3. Chen X, Liu L, Li Z..Cardiovascular protective effects and NO-mediated cerebro- vasore laxant effects of extract of ginkgo biloba leaves[J]. Zhonghua Yi Xue Za Zhi, 1998 Sep;78(9):692-5.
4. 薛锋, 顾玉东, 陈德松,等. 银杏叶提取物对大鼠去神经骨骼肌Ca2+ATP酶的保护作用. 医学研究生学报, 2002;15(2):125-127.
5. 薛锋, 顾玉东, 陈德松,等. 周围神经损伤后银杏叶提取物EGb761对感觉神经元的保护作用.复旦学报(医学版),2002;29(4):251-254.
6. 张烽, 顾玉东, 徐建光,等. 银杏叶提取物促进大鼠坐骨神经再生的实验研究. 中华显微外科杂志, 2000;11(4): 279-281.
7. 张玲, 胡金兰, 孔德虎,等.银杏叶提取物对豚鼠腹腔神经节细胞生物电的影响.安徽医科大学学报, 2002;37(2):99-102.
8. Mo N, Wallis DI, Watson A.Properties of putative cardiac and non-cardiac neurons in the rat stellate ganglion.J Auton Nerv Syst,1994; 47(1-2):7-22.
9. 杨文浩, 张蕴平, 刘守彦. 配制不同浓度的二氧化碳和氧的方法. 河南医学院学报, 1984;19(4):64-66.
10. Shepherd GM.著, 蔡南山编译. 神经生物学,上海复旦大学出版社1992第一版: 62-63.
11. Mo N.Depolarization induced by and calcium-dependent after-hyperpolarization suppressed by muscarine in rat stellate ganglion neurons.Chinese Journal of
Pharmacology and Toxicology,1996 Feb;10(1):12-16.
12. Nishi S.The peripherial neurous system. Hubbard J.I.ed.N.Y.Plenum:225-255.
13. 韩济深主编. 神经科学原理, 北京医科大学出版社1999年第二版:222-239.
14. Smith PF,Maclennan K,Darlington CL.The neuriprotective properties of Ginkgo- biloba leaf:a review of the possible relation ship to platelet-activating factor(PAF).J Ethnopharmacol,1996 ; 50:131-9.
15. 胡波, 邓学军, 梅元武,等. 银杏叶提取物快速抑制谷氨酸诱导大鼠海马神经元内游离钙浓度升高的作用及特征. 中华老年心脑血管病杂志,2001; 3(3):164.
16. Nishida S,Satoh H.Mechanisms for the vasodilations induced by Ginkgo biloba extract and its main constituent, bilobalide, in rat aorta.Life Sci,2003 Apr 25;72(23): 2659-2667.
17. Das A, Shanker G, Nath C,et al. A comparative study in rodents of standardized extracts of Bacopa monniera and Ginkgo biloba. Anticholinesterase and cognitive enhancing activities.Pharmacol Biochem Behav,2002 Nov;73(4):893-900.
18. Taylor JE.Neuromediator binding to receptors in the rat brain. The effect of chronic administration of Ginkgo biloba extract. Presse Med,1986 Sep 25;15(31):1491-3.
19. DeFeudis FV, Drieu K. Ginkgo biloba extract (EGb 761) and CNS functions: basic studies and clinical applications. Curr Drug Targets,2000 Jul;1(1):25-58.
20. Commissiong J W. Monoamine Metabolites:Their Relationship and Lack of Relationship to Monoaminergic Neuronal Activity [J]. Biochem Pharmacol,1985; 34:1127.
21. Zhu Li, Wu Juan,Liao Hong, et al. Antagonistic effects of extract from leaves of Ginkgo biloba on glutamate neurotoxicity.Zhongguo Yaoli Xuebao,1997;18(4):344.
22. 朱克主编.神经病学?自主神经系统疾病,人民军医出版2001年第一版:139- 140.
23. Sasaki Y, Noguchi T, Yamamoto E.et al.Effects of Ginkgo biloba extract (EGb 761) on cerebral thrombosis and blood pressure in stroke-prone spontaneously hypertensive rats. Clin Exp Pharmacol Physiol,2002 Nov;29(11):963-7.
24. Stucher O,Pons C,Duverger JP,et al.Effect of Ginkgobloba extract (EGb761) on the vasospastic response of mouse cutaneous arterioles to plateletactivation. Int J Mictocirc Clin EXP,1997;17(2):61.
25. Stucker O, Pons C, Duverger JP,et al.Effects of Ginkgo biloba extract (EGb 761) on arteriolar spasm in a rat cremaster muscle preparation. Int J Microcirc Clin Exp,1996 Mar-Apr;16(2):98-104.
26. Cheung F, Siow YL, O K.Inhibition by ginkgolides and bilobalide of the production of nitric oxide in macrophages (THP-1) but not in endothelial cells (HUVEC). Biochem Pharmacol, 2001 Feb 15;61(4):503-10.
27. Kubota Y, Tanaka N, Umegaki K,et al. Ginkgo biloba extract-induced relaxation of rat aorta is associated with increase in endothelial intracellular calcium level.Life Sci, 2001 Oct 5;69(20):2327-36.
28. Dudel J. Transmitter release triggered by a local depolarization in motor nerve terminals of the frog: role of calcium entry and of depolarization.Neurosci Lett,1983 Oct 31;41(1-2):133-8.
29. 韩济深主编. 神经科学原理, 北京医科大学出版社1999年第二版:294-304.
30. Zhu L, Gao J, Wang Y,et al.J Neuron degeneration induced by verapamil and attenuated by EGb761. Basic Clin Physiol Pharmacol,1997;8(4):301-14.
2. Lagente V, Boichot E, Carre C,et al. Effects of the platelet activating factor ant- agonists BN 52021 and BN 50730 on antigen-induced bronchial hyperresponsiveness and eosinophil infiltration in lung from sensitized guinea-pigs[J]. Clin Exp Allergy, 1993 Dec;23(12):1002-10.
3. Chen X, Liu L, Li Z..Cardiovascular protective effects and NO-mediated cerebro- vasore laxant effects of extract of ginkgo biloba leaves[J]. Zhonghua Yi Xue Za Zhi, 1998 Sep;78(9):692-5.
4. 薛锋, 顾玉东, 陈德松,等. 银杏叶提取物对大鼠去神经骨骼肌Ca2+ATP酶的保护作用. 医学研究生学报, 2002;15(2):125-127.
5. 薛锋, 顾玉东, 陈德松,等. 周围神经损伤后银杏叶提取物EGb761对感觉神经元的保护作用.复旦学报(医学版),2002;29(4):251-254.
6. 张烽, 顾玉东, 徐建光,等. 银杏叶提取物促进大鼠坐骨神经再生的实验研究. 中华显微外科杂志, 2000;11(4): 279-281.
7. 张玲, 胡金兰, 孔德虎,等.银杏叶提取物对豚鼠腹腔神经节细胞生物电的影响.安徽医科大学学报, 2002;37(2):99-102.
8. Mo N, Wallis DI, Watson A.Properties of putative cardiac and non-cardiac neurons in the rat stellate ganglion.J Auton Nerv Syst,1994; 47(1-2):7-22.
9. 杨文浩, 张蕴平, 刘守彦. 配制不同浓度的二氧化碳和氧的方法. 河南医学院学报, 1984;19(4):64-66.
10. Shepherd GM.著, 蔡南山编译. 神经生物学,上海复旦大学出版社1992第一版: 62-63.
11. Mo N.Depolarization induced by and calcium-dependent after-hyperpolarization suppressed by muscarine in rat stellate ganglion neurons.Chinese Journal of
Pharmacology and Toxicology,1996 Feb;10(1):12-16.
12. Nishi S.The peripherial neurous system. Hubbard J.I.ed.N.Y.Plenum:225-255.
13. 韩济深主编. 神经科学原理, 北京医科大学出版社1999年第二版:222-239.
14. Smith PF,Maclennan K,Darlington CL.The neuriprotective properties of Ginkgo- biloba leaf:a review of the possible relation ship to platelet-activating factor(PAF).J Ethnopharmacol,1996 ; 50:131-9.
15. 胡波, 邓学军, 梅元武,等. 银杏叶提取物快速抑制谷氨酸诱导大鼠海马神经元内游离钙浓度升高的作用及特征. 中华老年心脑血管病杂志,2001; 3(3):164.
16. Nishida S,Satoh H.Mechanisms for the vasodilations induced by Ginkgo biloba extract and its main constituent, bilobalide, in rat aorta.Life Sci,2003 Apr 25;72(23): 2659-2667.
17. Das A, Shanker G, Nath C,et al. A comparative study in rodents of standardized extracts of Bacopa monniera and Ginkgo biloba. Anticholinesterase and cognitive enhancing activities.Pharmacol Biochem Behav,2002 Nov;73(4):893-900.
18. Taylor JE.Neuromediator binding to receptors in the rat brain. The effect of chronic administration of Ginkgo biloba extract. Presse Med,1986 Sep 25;15(31):1491-3.
19. DeFeudis FV, Drieu K. Ginkgo biloba extract (EGb 761) and CNS functions: basic studies and clinical applications. Curr Drug Targets,2000 Jul;1(1):25-58.
20. Commissiong J W. Monoamine Metabolites:Their Relationship and Lack of Relationship to Monoaminergic Neuronal Activity [J]. Biochem Pharmacol,1985; 34:1127.
21. Zhu Li, Wu Juan,Liao Hong, et al. Antagonistic effects of extract from leaves of Ginkgo biloba on glutamate neurotoxicity.Zhongguo Yaoli Xuebao,1997;18(4):344.
22. 朱克主编.神经病学?自主神经系统疾病,人民军医出版2001年第一版:139- 140.
23. Sasaki Y, Noguchi T, Yamamoto E.et al.Effects of Ginkgo biloba extract (EGb 761) on cerebral thrombosis and blood pressure in stroke-prone spontaneously hypertensive rats. Clin Exp Pharmacol Physiol,2002 Nov;29(11):963-7.
24. Stucher O,Pons C,Duverger JP,et al.Effect of Ginkgobloba extract (EGb761) on the vasospastic response of mouse cutaneous arterioles to plateletactivation. Int J Mictocirc Clin EXP,1997;17(2):61.
25. Stucker O, Pons C, Duverger JP,et al.Effects of Ginkgo biloba extract (EGb 761) on arteriolar spasm in a rat cremaster muscle preparation. Int J Microcirc Clin Exp,1996 Mar-Apr;16(2):98-104.
26. Cheung F, Siow YL, O K.Inhibition by ginkgolides and bilobalide of the production of nitric oxide in macrophages (THP-1) but not in endothelial cells (HUVEC). Biochem Pharmacol, 2001 Feb 15;61(4):503-10.
27. Kubota Y, Tanaka N, Umegaki K,et al. Ginkgo biloba extract-induced relaxation of rat aorta is associated with increase in endothelial intracellular calcium level.Life Sci, 2001 Oct 5;69(20):2327-36.
28. Dudel J. Transmitter release triggered by a local depolarization in motor nerve terminals of the frog: role of calcium entry and of depolarization.Neurosci Lett,1983 Oct 31;41(1-2):133-8.
29. 韩济深主编. 神经科学原理, 北京医科大学出版社1999年第二版:294-304.
30. Zhu L, Gao J, Wang Y,et al.J Neuron degeneration induced by verapamil and attenuated by EGb761. Basic Clin Physiol Pharmacol,1997;8(4):301-14.