芍药甙调节Oddi括约肌肌细胞运动及钾离子通道机制的研究
|
摘要
背景:Oddi括约肌(sphincter of Oddi,SO)位于胆管、胰管和十二指肠结合部,是胆汁和胰液的最终流出道。由胆总管括约肌、壶腹部括约肌、胰管括约肌和纵肌束组成。Oddi括约肌运动是一个动态的周期性变化过程并于十二指肠移动性运动复合波密切相关。具有将胆汁胰液排入十二指肠、防止十二指肠内容物返流至胆管和胰管内以及充盈胆囊的作用。因此Oddi括约肌的运动功能是胆道系统动力学研究的重要内容。Oddi括约肌运动功能障碍( sphincter of Oddi dysfunction ,SOD)是临床常见疾病之一,较难诊断和治疗。分为Oddi括约肌功能紊乱和Oddi括约肌狭窄两大类。Oddi括约肌功能紊乱主要是因为SO的持续痉挛造成的。严重的影响了人们的生活质量,目前尚无完全有效治疗方法。
目前国内外的文献就胃肠平滑肌运动机制的研究比较多,关于SO的运动机制及其中药的作用研究甚少。已有文献报道证实芍药甙对可以通过多种途径对胃肠平滑肌进行调解1,Oddi括约肌同属消化道平滑肌,芍药甙是否具有相同或是相似的调节途径对Oddi括约肌平滑肌进行调节。我们已经开展了对芍药甙对Oddi括约肌肌环运动的研究,并取得了一定的进展。结果显示芍药甙能够明显的抑制钾通道阻滞剂对家兔离体Oddi括约肌肌环的收缩作用,为了深入研究芍药甙的作用机理,我们提取单个Oddi括约肌肌细胞,直接观察芍药甙对平滑肌细胞的收缩和舒张活动的调节作用,以及钾离子通道的作用机制。从而在细胞水平上进一步阐明芍药甙对家兔Oddi括约肌运动调节的机制和途径。
目的:探讨电压依赖性钾通道(Kv )、ATP敏感性钾通道(KATP)以及大电导钙激活钾通道(BKca)对家兔Oddi括约肌平滑肌细胞的作用;探讨芍药甙对家兔Oddi括约肌细胞的调控作用。
方法:1.取纯种新西兰兔SO段,用Ⅱ型胶原酶消化获得单个平滑肌细胞,进行原代培养,免疫组织化学方法鉴定;并通过图像分析系统测定静息状态细胞长度。
2.观察Kv通道阻断剂4-aminopyridine (4-AP),KATP阻断剂Glib, BKca通道阻断剂Iberiotoxin (IBTX),对家兔Oddi括约肌平滑肌细胞的作用;观察芍药甙对电压依赖性钾通道(Kv )和大电导钙激活钾通道(BKca)阻断剂收缩作用的影响。
结果:1.家兔SO平滑肌细胞平均长度为(143.7±12.3)μm;
2.Kv通道阻断剂4-AP可以引起家兔Oddi括约肌平滑肌细胞收缩;并且随4-AP浓度增加,收缩程度增强;
3.BKca通道阻断剂IBTX能够轻度引起家兔Oddi括约肌平滑肌细胞收缩;
4. KATP阻断剂Glib引起家兔Oddi括约肌肌细胞收缩未见统计学意义;
5. 4-AP对兔胆道口平滑肌细胞的收缩作用能够被芍药甙抑制,并随浓度增加,抑制作用增强;
6. IBTX对兔胆道口平滑肌细胞的收缩作用能够被芍药甙抑制,并随浓度增加,抑制作用增强;
结论:1. Oddi括约肌平滑肌细胞是贴壁细胞,呈梭形外观。
2.Kv通道、BKca通道和KATP通道存在于家兔Oddi括约肌平滑肌细胞细胞膜表面。Kv通道和BKca通道在维持Oddi括约肌细胞的静息电位起主要作用。
3.芍药甙可能通过对Kv通道和BKca通道的调控,细胞膜静息电位的改变,实现对平滑肌的舒张效应。
Background : The sphincter of Oddi is located in the combine part of bile duct, duodenum and pancreatic duct. It is the final outflow tract of bile and pancreatic juice,consisting of four parts: biliary duct sphincter, pancreatic duct sphincter, ampullary sphincter and Longitudinal muscles. The sphincter of Oddi has a cyclic motility that is closely associated with the duodenal migrating motor complex. The sphincter of Oddi has three main functions: the regulation of flow into the duodenum, prevention of reflux from the duodenum to the bile and pancreatic duct, and filling of the gallbladder. Therefore, Oddi muscle movement is biliary dynamics research important content. sphincter of Oddi dysfunction is a digestive disease which is difficult to diagnose in time and treat properly, tending to divide it into sphincter of Oddi dyskinesia and sphincter of Oddi stenosis. Sphincter of Oddi dyskinesia is caused mainly by the lasting convulsion of SO. SOD affects the quality of life seriously. At present there is no completely effective treatment methods.
At home and abroad about the roles of the movement mechanism of gastrointestinal research literature more, but on the sphincter of Oddi mechanism study also relatively small. China has studied the Chinese peony active ingredients proven through a variety of ways paeoniflorin gastrointestinal smooth muscle relaxation, while paeoniflorin whether the same relaxing effect the sphincter of Oddi the same signal transduction mechanism, currently no relevant reports. We investigate the effects of Paeoniflorin on Oddi muscle movement and have achieved some progress. Paeoniflorin significantly inhibit the sphincter muscle ring′s constriction caused from potassium channel blockers. In order to research Paeoniflorin′s mechanism further, We observe Paeoniflorin to smooth muscle cells′s contraction and relaxation activity of direct action, in a single Oddi sphincter smooth muscle cells and. The effects and mechanisms and cellular signal transduction pathways of paeoniflorin are clarified clearly on isolated smooth muscle cells.
Objective : To investigate the regulating role of voltage-gated potassium channels(Kv), large-conductance calcium-activated potassium channels(BKca), ATP-sensitive K+ channels(KATP) on Oddi 's Sphincter muscle cells in the rabbits, and the effects of paeoniflorin.
Methods: Oddi 's Sphincter muscle cells were isolated from the muscle layers of Oddi 's Sphincter from rabbits. Original generation training, immunohistochemical method appraisal; Through the image analysis systems measure length in the resting state. Blockers of different type of potassium channels were applied , the lengh of cell was measured by computerized image micrometry.
Results:
1. The average length of SO smooth muscle cells is (143.7 + 12.3)μm.
2. 4-aminopyridine (4-AP), a blocker of Kv channels, induced Oddi's Sphincter muscle cells contraction in a dose-dependent manner.
3. Iberiotoxin (IBTX),another blocker of BKCa channels, had slightly contractile effects on smooth muscle cells.
4.There were no contractile effects observed by application of glibenclamide (Glib), a blocker of KATP channels.
5.Contraction induced by 4-AP was inhibited by paeoniflorin in a concentrateion- dependent manner.
6.Contraction induced by IBTX was inhibited by paeoniflorin in a concentrateion- dependent manner.
Conclusion:
1. The smooth muscle cell of sphincter of Oddi is to stick wall cells, with a spindle shape appearance.
2.There are voltage-gated potassium channel, calcium-activiated potassium channel and ATP-sensitive potassium channels in the membrane of the smooth muscle cell of SO. In resting condition, voltage-gated potassium channel and calcium-activiated potassium channel played role in controlling membrane potential of Oddi's Sphincter muscle cells.
3.By regulating voltage-gated potassium channel and calcium-activiated potassium channel,changing the membrane potential of muscle cells ,paeoniflorin cause relaxation of smooth muscle cell possibly.
目前国内外的文献就胃肠平滑肌运动机制的研究比较多,关于SO的运动机制及其中药的作用研究甚少。已有文献报道证实芍药甙对可以通过多种途径对胃肠平滑肌进行调解1,Oddi括约肌同属消化道平滑肌,芍药甙是否具有相同或是相似的调节途径对Oddi括约肌平滑肌进行调节。我们已经开展了对芍药甙对Oddi括约肌肌环运动的研究,并取得了一定的进展。结果显示芍药甙能够明显的抑制钾通道阻滞剂对家兔离体Oddi括约肌肌环的收缩作用,为了深入研究芍药甙的作用机理,我们提取单个Oddi括约肌肌细胞,直接观察芍药甙对平滑肌细胞的收缩和舒张活动的调节作用,以及钾离子通道的作用机制。从而在细胞水平上进一步阐明芍药甙对家兔Oddi括约肌运动调节的机制和途径。
目的:探讨电压依赖性钾通道(Kv )、ATP敏感性钾通道(KATP)以及大电导钙激活钾通道(BKca)对家兔Oddi括约肌平滑肌细胞的作用;探讨芍药甙对家兔Oddi括约肌细胞的调控作用。
方法:1.取纯种新西兰兔SO段,用Ⅱ型胶原酶消化获得单个平滑肌细胞,进行原代培养,免疫组织化学方法鉴定;并通过图像分析系统测定静息状态细胞长度。
2.观察Kv通道阻断剂4-aminopyridine (4-AP),KATP阻断剂Glib, BKca通道阻断剂Iberiotoxin (IBTX),对家兔Oddi括约肌平滑肌细胞的作用;观察芍药甙对电压依赖性钾通道(Kv )和大电导钙激活钾通道(BKca)阻断剂收缩作用的影响。
结果:1.家兔SO平滑肌细胞平均长度为(143.7±12.3)μm;
2.Kv通道阻断剂4-AP可以引起家兔Oddi括约肌平滑肌细胞收缩;并且随4-AP浓度增加,收缩程度增强;
3.BKca通道阻断剂IBTX能够轻度引起家兔Oddi括约肌平滑肌细胞收缩;
4. KATP阻断剂Glib引起家兔Oddi括约肌肌细胞收缩未见统计学意义;
5. 4-AP对兔胆道口平滑肌细胞的收缩作用能够被芍药甙抑制,并随浓度增加,抑制作用增强;
6. IBTX对兔胆道口平滑肌细胞的收缩作用能够被芍药甙抑制,并随浓度增加,抑制作用增强;
结论:1. Oddi括约肌平滑肌细胞是贴壁细胞,呈梭形外观。
2.Kv通道、BKca通道和KATP通道存在于家兔Oddi括约肌平滑肌细胞细胞膜表面。Kv通道和BKca通道在维持Oddi括约肌细胞的静息电位起主要作用。
3.芍药甙可能通过对Kv通道和BKca通道的调控,细胞膜静息电位的改变,实现对平滑肌的舒张效应。
Background : The sphincter of Oddi is located in the combine part of bile duct, duodenum and pancreatic duct. It is the final outflow tract of bile and pancreatic juice,consisting of four parts: biliary duct sphincter, pancreatic duct sphincter, ampullary sphincter and Longitudinal muscles. The sphincter of Oddi has a cyclic motility that is closely associated with the duodenal migrating motor complex. The sphincter of Oddi has three main functions: the regulation of flow into the duodenum, prevention of reflux from the duodenum to the bile and pancreatic duct, and filling of the gallbladder. Therefore, Oddi muscle movement is biliary dynamics research important content. sphincter of Oddi dysfunction is a digestive disease which is difficult to diagnose in time and treat properly, tending to divide it into sphincter of Oddi dyskinesia and sphincter of Oddi stenosis. Sphincter of Oddi dyskinesia is caused mainly by the lasting convulsion of SO. SOD affects the quality of life seriously. At present there is no completely effective treatment methods.
At home and abroad about the roles of the movement mechanism of gastrointestinal research literature more, but on the sphincter of Oddi mechanism study also relatively small. China has studied the Chinese peony active ingredients proven through a variety of ways paeoniflorin gastrointestinal smooth muscle relaxation, while paeoniflorin whether the same relaxing effect the sphincter of Oddi the same signal transduction mechanism, currently no relevant reports. We investigate the effects of Paeoniflorin on Oddi muscle movement and have achieved some progress. Paeoniflorin significantly inhibit the sphincter muscle ring′s constriction caused from potassium channel blockers. In order to research Paeoniflorin′s mechanism further, We observe Paeoniflorin to smooth muscle cells′s contraction and relaxation activity of direct action, in a single Oddi sphincter smooth muscle cells and. The effects and mechanisms and cellular signal transduction pathways of paeoniflorin are clarified clearly on isolated smooth muscle cells.
Objective : To investigate the regulating role of voltage-gated potassium channels(Kv), large-conductance calcium-activated potassium channels(BKca), ATP-sensitive K+ channels(KATP) on Oddi 's Sphincter muscle cells in the rabbits, and the effects of paeoniflorin.
Methods: Oddi 's Sphincter muscle cells were isolated from the muscle layers of Oddi 's Sphincter from rabbits. Original generation training, immunohistochemical method appraisal; Through the image analysis systems measure length in the resting state. Blockers of different type of potassium channels were applied , the lengh of cell was measured by computerized image micrometry.
Results:
1. The average length of SO smooth muscle cells is (143.7 + 12.3)μm.
2. 4-aminopyridine (4-AP), a blocker of Kv channels, induced Oddi's Sphincter muscle cells contraction in a dose-dependent manner.
3. Iberiotoxin (IBTX),another blocker of BKCa channels, had slightly contractile effects on smooth muscle cells.
4.There were no contractile effects observed by application of glibenclamide (Glib), a blocker of KATP channels.
5.Contraction induced by 4-AP was inhibited by paeoniflorin in a concentrateion- dependent manner.
6.Contraction induced by IBTX was inhibited by paeoniflorin in a concentrateion- dependent manner.
Conclusion:
1. The smooth muscle cell of sphincter of Oddi is to stick wall cells, with a spindle shape appearance.
2.There are voltage-gated potassium channel, calcium-activiated potassium channel and ATP-sensitive potassium channels in the membrane of the smooth muscle cell of SO. In resting condition, voltage-gated potassium channel and calcium-activiated potassium channel played role in controlling membrane potential of Oddi's Sphincter muscle cells.
3.By regulating voltage-gated potassium channel and calcium-activiated potassium channel,changing the membrane potential of muscle cells ,paeoniflorin cause relaxation of smooth muscle cell possibly.
引文
1.于文胜,马涛,刘健,齐清会。芍药甙对胃肠平滑肌细胞动力的影响及其信号转导途径的研究。基础医学与临床,2003s1:111。
2.雒建瑞,王长森,傅雷,孙艺平。芍药甙对家兔离体Oddi括约肌肌环收缩活动的影响[J]。大连医科大学学报,2009,31 ( 6) : 668-671.
3.刘培庆,鲁伟。肌肉组织的体外培养。体外培养的原理与技术,第一版。北京:科学出版社,2001, 636-643.
4.郭兰忠。现代实用中药学,人民卫生出版社,1999年6月,895-897.
5.翁小刚,聂淑琴,黄璐琦。芍药科植物的研究概况,中国试验方剂学杂志,2003, 9:55-59.
6.王朝虹,IA知大。芍药化学成分及药理研究,时珍国医国药,1999, 10(7) : 544-566.
7. Vogalis F. Potassium channels in gastrointestinal smooth muscle. J Auton Pharmacol, 2000, 20: 207-219.
8. Feranchak AP. Ion channels in digestive health and disease .J Pediatr Gastroenterol Nutr.2003, 37:230-241.
9. Kim Lawson. Potassium channel openers as potential therapeutic weapons2000, 57:838-845.
10. Du C ,Carl A ,Smith TK , et al. Mechanism of cyclic AMP-induced hyper polarization in canine colon. J Pharmacol Exp Therap 1994, 268: 208-215.
11. Huizinga JD, Stern H, Chow E, et al. Electrophysiological control of motility in the human colon. Gastroenterology, 1985, 88 500-511.
12. Sanders KM. Ionic mechanisms of electrical rhythmicity in gastrointestinal smooth muscles. Annual Review of Physiology, 1992 54:439-453.
13.刘先胜,徐永健,张珍祥等.钾通道在大鼠支气管平滑肌张力调控中作用的研究,中国应用生理学杂志,2003:19(1): 48-51.
14. Nelson MT, Patlak JB ,Worley JF, Standen NB Calcium channels, potassium channels, and voltage dependence of arterial smooth muscle tone [J]. Am JPhysiol Cell Physiol,1990a,259(1 Pt 1):C3-C18.
15. Nelson MT, Quayle JM. Physiological roles and properties of potassium channels in arterial smooth muscle [J].Am J Physiol , 1995, 268:C799-C822.
16. Jackson WF. Potassium channels and regulation of the microcirculation [J].Microcirculation, 1998, 5:85-90.
17. Jackson WF, Blair KL. Characterization and function of Cat十一activated K+ channels in hamster cremasteric arteriolar muscle cells [J]. Ain J Physiol Heart Cir Physiol, 1998a, 274:H27-H34.
18. Berridge MJ, Bootman MD, Lipp P. Calcium: a life and death signal. Nature, 1998, 395:645-648.
19. Tsien RW, Tsien RY. Calcium channels, stores and oscillations. Annu Rev Cell Biol 1990, 6: 715-760.
20. Clapham DE .Calcium signaling[J』. Cell . 1995 , 80:259-268.
21. Berridge MJ, Bootman MD, Lipp .Caleium: a life and death signal [J].Nature, 1998, 395:645-648.
22. Tsien RW , Tsien RY .Caleium channels, stores and oscillations [J]. Annu Rev Cell Biol, 1990, 6:715-760.
23. Andrew PS, Avril VS. Signal transduction and regulation in smooth muscle. Nautre . 1994, 372: 231-236.
24. Sanders KM, Invited review. Mechanisms of calcium handling in smooth muscles[J].J Appl Physiol, 2001, 91:1438-1449.
25. Jacques D, Sader S, Hassan G, Shbaklo H. Neuropeptide Y induced increase of cytosolic and nuclear Ca z+ in heart and vascular smooth muscle cells [J].Can J Physiol Pharmacol, 2000, 78:162- 172.
26. Bolton .TB , SA, Zholos AV, Gordienko DV. Excitation-contractioncoupling in gastrointestinal and other smooth muscles [J].Annu Rev Physiol,1999, 61:85-115.
27. Makhlouf GM, Murthy KS.Signal transduction in gastrointestinal smooth muscle [j].Cell Signal,1997,9:269-276.
28. Koh SD,Contribution of delayed rectifier potassium currents to the electrical activity of murine colonic smooth muscle . J Physiol,1999,515:475-487.
29. Evangelos D,Michelakis et al. Potassium channels reuglate. Tone in rat Pulmonary veins .Am J Physiol Lung Cell Mol Physiol,2001,280:1138-1147.
30. Amberg GC,RossowCF,NavedoMF,SnatnaaLF.NFATe3 Regulates Kv2.l Expression in Arterial Smooth Muscle .J Bio Chem.2004,279:47326-47334.
1. Bosch A, Pena LR. The sphincter of Oddi [J] . Dig Dis Sci, 2007, 52(5):1211-1218.
2. Stuart Sherman , Glen A Lehman et al. Sphincter of Odd dysfunction : Diagnosised Treatiment JOP [J].Pancreas(online), 2001,2(6):382-400.
3. Boyden,E.A.The anatomy of the choledochoduodenal junction in man.Surg. Gynecol.Obstet, 1957,104:641-652.
4. Woods CM, Mawe GM, Toouli J, et al. The sphincter of Oddi: understanding its control and function[J]. Neurogastroenterol Motil,2005,17:31-40.
5. Moises Guelrud MD ,et al Sphincter of Oddi manometry in healthy volunteers . Digestive Diseases and Sciences,1990;35(1);38.
6. Honda R,Toouli J,Dodds WJ,Sarna S,Hogan WJ,Itoh ZRelationship of sphincter of Oddi spike bursts to gastrointestinal myoelectric activity in consciousopossums[J].Clin Invest,1982,69(3): 770-778.
7.黄悦,陈飞,于彬.豚鼠壶腹Cajal样细胞的分布及Oddi括约肌肌电活动观察[J].解放军医学杂志,2008,33(9):1069-1073.
8. Worthley CS,Baker RA,Iannos J,Saccone GT,Toouli J.Human fasting and postprandial sphincter of Oddi motility[J].Br J Surg 1989,76(1):706–714.
9. Liu CY, Liu JZ,Lt ZY,Liu KJ. The vagus nerve coordinates the motion of gallbladder and sphincter of Oddi in the interdigestive period in rabbits. 2000;16:347349.
10. Dhalstrand C, Edin R, Dahlstrom A et al.An in-vivo model for the simultaneous study of motility of the gallbladder, Sphincter of Oddi and duodena wall in the cat. Acta Physiol. Scand. 1985; 123: 355.
11. Para japati DN, Hogan W J . Sphincter of Oddi dysfunction and other functional biliary disorders + evaluation and treatment [ J]. Gastroenterol Clin N Am, 2003, 32 ( 2 ) : 601– 618.
12. Vogalis F, Smith TK. Functional innervation of the biliary sphincter of the guinea-pig revealed by anti-autonomic drugs. J Auton Pharmacol. 2000 Jun; 20(3):177-83.
13. AbriruH,SarnaSK,CondonRE,etalGastroenterology.Gastroenterology,1994;106(6) 1652~1661.
14. Krishnamurthy GT.Krishnamurthy S.Watson RD.Characterization of basalhepatic bile flow and the effects Of intravenous cholecystokinin on the sphincter and gallbladder in patients with sphincter of Oddi spasm[J].Eur Med Mol Imaging. 2004,31(3):85-93.
15. Woods C M.GM.Shaffer EA.et al.Effects of bioactive agents On biliary motor function[J].Curr Gastroenterol Rep,2003,5(1):151-159.
16. Jia Qing Huang.Somafostatin stimulate the brush-tailed Possum sphincter of Oddi invivo.Gastroenterology,1998,l15:672-679.
17.周吕,柯美云,胃肠动力学基础与临床.北京科学出版社,1999:149.
18. Thune A, Saccone GTP, Toouli J et al. Distention of the gallbladder inhibits Sphincter of Oddi motility in man. Gut 1991; 32: 690.
19. Fazel A,Burton FR.Endoscopy,2002;34(1),78~81.
20. Baker RA,Saccone GTP.Dig Dis Sci,1990;35(6),711~715.
21.锥建瑞,王长森,傅雷,孙艺平.芍药甙对家兔离体Oddi括约肌肌环收缩活动的影响[J].大连医科大学学报,2009, 31 ( 6) : 668-671.
22. Tzovaras G, Rowlands BJ. Diagnosis and treatmentof sphincter of Oddi dysfunction. Br J Surg 1998; 85:588-595.
23.许国铭,邹多武. Odd i括约肌运动功能障碍的诊断和治疗[ J] .临床内科杂志, 1999, 16 ( 2 ): 67- 69.
24.邹多武.功能性胃肠病罗马标准解读:胆囊及Oddi括约肌功能紊乱.临床消化病杂志,2006,18:262-263.
25. Cheon YK, Cho YD, Moon JH, et al. Effects of vardenafil, a phosphodiesterase type-5 inhibitor, on sphincter of Oddi motility in patients with suspected biliary sphincter of Oddi dysfunction[J]. Gastrointest Endosc,2009,69(6):1111-1116.
26. Guelrud M,Mendoza S,Rossiter G,et al1 Sphincter of Oddi manometry in healthy volunteers1 Dig Dis Sci,1990,35(1):38-46.
27. FgTzovaras G , Rowlands BJ [ J] Br J Surg, 1998, 85( 5) : 588~595.
28. Cheon YK, Cho YD, Moon JH, et al. Effects of vardenafil, a phosphodiesterase type-5 inhibitor, on sphincter of Oddi motility in patients with suspected biliary sphincter of Oddi dysfunction[J]. Gastrointest Endosc,2009,69(6):1111-1116.
29. Fullarton GM ,Falconer S,Falconer F,et a1.Gut,1992 ; 33:550～553.
30.许国铭,邹多武,李兆申,等胃肠病学.1996;1:17~19.
31. James Toouli Journal of Gastroenterology and Hepatology 2009;24;57~62.
32. Wehrmann T, Seifert H, Seipp M, Lembcke B,Caspary WF. Endoscopic injection of botulinum toxin for biliary sphincter of Oddi dysfunction. Endoscopy 1998; 30: 702-707.
2.雒建瑞,王长森,傅雷,孙艺平。芍药甙对家兔离体Oddi括约肌肌环收缩活动的影响[J]。大连医科大学学报,2009,31 ( 6) : 668-671.
3.刘培庆,鲁伟。肌肉组织的体外培养。体外培养的原理与技术,第一版。北京:科学出版社,2001, 636-643.
4.郭兰忠。现代实用中药学,人民卫生出版社,1999年6月,895-897.
5.翁小刚,聂淑琴,黄璐琦。芍药科植物的研究概况,中国试验方剂学杂志,2003, 9:55-59.
6.王朝虹,IA知大。芍药化学成分及药理研究,时珍国医国药,1999, 10(7) : 544-566.
7. Vogalis F. Potassium channels in gastrointestinal smooth muscle. J Auton Pharmacol, 2000, 20: 207-219.
8. Feranchak AP. Ion channels in digestive health and disease .J Pediatr Gastroenterol Nutr.2003, 37:230-241.
9. Kim Lawson. Potassium channel openers as potential therapeutic weapons2000, 57:838-845.
10. Du C ,Carl A ,Smith TK , et al. Mechanism of cyclic AMP-induced hyper polarization in canine colon. J Pharmacol Exp Therap 1994, 268: 208-215.
11. Huizinga JD, Stern H, Chow E, et al. Electrophysiological control of motility in the human colon. Gastroenterology, 1985, 88 500-511.
12. Sanders KM. Ionic mechanisms of electrical rhythmicity in gastrointestinal smooth muscles. Annual Review of Physiology, 1992 54:439-453.
13.刘先胜,徐永健,张珍祥等.钾通道在大鼠支气管平滑肌张力调控中作用的研究,中国应用生理学杂志,2003:19(1): 48-51.
14. Nelson MT, Patlak JB ,Worley JF, Standen NB Calcium channels, potassium channels, and voltage dependence of arterial smooth muscle tone [J]. Am JPhysiol Cell Physiol,1990a,259(1 Pt 1):C3-C18.
15. Nelson MT, Quayle JM. Physiological roles and properties of potassium channels in arterial smooth muscle [J].Am J Physiol , 1995, 268:C799-C822.
16. Jackson WF. Potassium channels and regulation of the microcirculation [J].Microcirculation, 1998, 5:85-90.
17. Jackson WF, Blair KL. Characterization and function of Cat十一activated K+ channels in hamster cremasteric arteriolar muscle cells [J]. Ain J Physiol Heart Cir Physiol, 1998a, 274:H27-H34.
18. Berridge MJ, Bootman MD, Lipp P. Calcium: a life and death signal. Nature, 1998, 395:645-648.
19. Tsien RW, Tsien RY. Calcium channels, stores and oscillations. Annu Rev Cell Biol 1990, 6: 715-760.
20. Clapham DE .Calcium signaling[J』. Cell . 1995 , 80:259-268.
21. Berridge MJ, Bootman MD, Lipp .Caleium: a life and death signal [J].Nature, 1998, 395:645-648.
22. Tsien RW , Tsien RY .Caleium channels, stores and oscillations [J]. Annu Rev Cell Biol, 1990, 6:715-760.
23. Andrew PS, Avril VS. Signal transduction and regulation in smooth muscle. Nautre . 1994, 372: 231-236.
24. Sanders KM, Invited review. Mechanisms of calcium handling in smooth muscles[J].J Appl Physiol, 2001, 91:1438-1449.
25. Jacques D, Sader S, Hassan G, Shbaklo H. Neuropeptide Y induced increase of cytosolic and nuclear Ca z+ in heart and vascular smooth muscle cells [J].Can J Physiol Pharmacol, 2000, 78:162- 172.
26. Bolton .TB , SA, Zholos AV, Gordienko DV. Excitation-contractioncoupling in gastrointestinal and other smooth muscles [J].Annu Rev Physiol,1999, 61:85-115.
27. Makhlouf GM, Murthy KS.Signal transduction in gastrointestinal smooth muscle [j].Cell Signal,1997,9:269-276.
28. Koh SD,Contribution of delayed rectifier potassium currents to the electrical activity of murine colonic smooth muscle . J Physiol,1999,515:475-487.
29. Evangelos D,Michelakis et al. Potassium channels reuglate. Tone in rat Pulmonary veins .Am J Physiol Lung Cell Mol Physiol,2001,280:1138-1147.
30. Amberg GC,RossowCF,NavedoMF,SnatnaaLF.NFATe3 Regulates Kv2.l Expression in Arterial Smooth Muscle .J Bio Chem.2004,279:47326-47334.
1. Bosch A, Pena LR. The sphincter of Oddi [J] . Dig Dis Sci, 2007, 52(5):1211-1218.
2. Stuart Sherman , Glen A Lehman et al. Sphincter of Odd dysfunction : Diagnosised Treatiment JOP [J].Pancreas(online), 2001,2(6):382-400.
3. Boyden,E.A.The anatomy of the choledochoduodenal junction in man.Surg. Gynecol.Obstet, 1957,104:641-652.
4. Woods CM, Mawe GM, Toouli J, et al. The sphincter of Oddi: understanding its control and function[J]. Neurogastroenterol Motil,2005,17:31-40.
5. Moises Guelrud MD ,et al Sphincter of Oddi manometry in healthy volunteers . Digestive Diseases and Sciences,1990;35(1);38.
6. Honda R,Toouli J,Dodds WJ,Sarna S,Hogan WJ,Itoh ZRelationship of sphincter of Oddi spike bursts to gastrointestinal myoelectric activity in consciousopossums[J].Clin Invest,1982,69(3): 770-778.
7.黄悦,陈飞,于彬.豚鼠壶腹Cajal样细胞的分布及Oddi括约肌肌电活动观察[J].解放军医学杂志,2008,33(9):1069-1073.
8. Worthley CS,Baker RA,Iannos J,Saccone GT,Toouli J.Human fasting and postprandial sphincter of Oddi motility[J].Br J Surg 1989,76(1):706–714.
9. Liu CY, Liu JZ,Lt ZY,Liu KJ. The vagus nerve coordinates the motion of gallbladder and sphincter of Oddi in the interdigestive period in rabbits. 2000;16:347349.
10. Dhalstrand C, Edin R, Dahlstrom A et al.An in-vivo model for the simultaneous study of motility of the gallbladder, Sphincter of Oddi and duodena wall in the cat. Acta Physiol. Scand. 1985; 123: 355.
11. Para japati DN, Hogan W J . Sphincter of Oddi dysfunction and other functional biliary disorders + evaluation and treatment [ J]. Gastroenterol Clin N Am, 2003, 32 ( 2 ) : 601– 618.
12. Vogalis F, Smith TK. Functional innervation of the biliary sphincter of the guinea-pig revealed by anti-autonomic drugs. J Auton Pharmacol. 2000 Jun; 20(3):177-83.
13. AbriruH,SarnaSK,CondonRE,etalGastroenterology.Gastroenterology,1994;106(6) 1652~1661.
14. Krishnamurthy GT.Krishnamurthy S.Watson RD.Characterization of basalhepatic bile flow and the effects Of intravenous cholecystokinin on the sphincter and gallbladder in patients with sphincter of Oddi spasm[J].Eur Med Mol Imaging. 2004,31(3):85-93.
15. Woods C M.GM.Shaffer EA.et al.Effects of bioactive agents On biliary motor function[J].Curr Gastroenterol Rep,2003,5(1):151-159.
16. Jia Qing Huang.Somafostatin stimulate the brush-tailed Possum sphincter of Oddi invivo.Gastroenterology,1998,l15:672-679.
17.周吕,柯美云,胃肠动力学基础与临床.北京科学出版社,1999:149.
18. Thune A, Saccone GTP, Toouli J et al. Distention of the gallbladder inhibits Sphincter of Oddi motility in man. Gut 1991; 32: 690.
19. Fazel A,Burton FR.Endoscopy,2002;34(1),78~81.
20. Baker RA,Saccone GTP.Dig Dis Sci,1990;35(6),711~715.
21.锥建瑞,王长森,傅雷,孙艺平.芍药甙对家兔离体Oddi括约肌肌环收缩活动的影响[J].大连医科大学学报,2009, 31 ( 6) : 668-671.
22. Tzovaras G, Rowlands BJ. Diagnosis and treatmentof sphincter of Oddi dysfunction. Br J Surg 1998; 85:588-595.
23.许国铭,邹多武. Odd i括约肌运动功能障碍的诊断和治疗[ J] .临床内科杂志, 1999, 16 ( 2 ): 67- 69.
24.邹多武.功能性胃肠病罗马标准解读:胆囊及Oddi括约肌功能紊乱.临床消化病杂志,2006,18:262-263.
25. Cheon YK, Cho YD, Moon JH, et al. Effects of vardenafil, a phosphodiesterase type-5 inhibitor, on sphincter of Oddi motility in patients with suspected biliary sphincter of Oddi dysfunction[J]. Gastrointest Endosc,2009,69(6):1111-1116.
26. Guelrud M,Mendoza S,Rossiter G,et al1 Sphincter of Oddi manometry in healthy volunteers1 Dig Dis Sci,1990,35(1):38-46.
27. FgTzovaras G , Rowlands BJ [ J] Br J Surg, 1998, 85( 5) : 588~595.
28. Cheon YK, Cho YD, Moon JH, et al. Effects of vardenafil, a phosphodiesterase type-5 inhibitor, on sphincter of Oddi motility in patients with suspected biliary sphincter of Oddi dysfunction[J]. Gastrointest Endosc,2009,69(6):1111-1116.
29. Fullarton GM ,Falconer S,Falconer F,et a1.Gut,1992 ; 33:550～553.
30.许国铭,邹多武,李兆申,等胃肠病学.1996;1:17~19.
31. James Toouli Journal of Gastroenterology and Hepatology 2009;24;57~62.
32. Wehrmann T, Seifert H, Seipp M, Lembcke B,Caspary WF. Endoscopic injection of botulinum toxin for biliary sphincter of Oddi dysfunction. Endoscopy 1998; 30: 702-707.