硫化氢对缺血豚鼠乳头肌的电生理效应
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摘要
硫化氢( Hydrogen Sulfide, H2S )是继一氧化氮( Nitric Oxide, NO )、一氧化碳( Carbon Monoxide, CO )之后的第三种内源性气体信号分子,发挥着重要的生理功能。内源性H2S可以由两种磷酸吡哚醛-5'-磷酸依赖性酶,即胱硫醚-β-合酶( cystathionie-β-sythase, CBS )和胱硫醚-γ-裂解酶( cystathionine-γ-lyase, CSE )催化生产。H2S可通过开放血管平滑肌细胞ATP敏感性钾离子通道( KATP通道)和抑制细胞外钙内流,发挥舒血管效应。ATP敏感性钾离子通道在心肌细胞中也有广泛分布,其开放是一种重要的心脏内源性保护机制。近来有研究表明,H2S可以通过KATP通道在心脏中发挥负性肌力作用,而且可以由心脏组织内源性产生,调节心脏功能。在硫化氢对心肌细胞电生理的研究中已发现,正常生理环境中外源性地给予H2S可缩短乳头状肌细胞的动作电位时程,对部分去极化的乳头状肌细胞还可降低动作电位幅值和超射值,减慢零相最大上升速度。但目前,关于H2S对于缺血环境下心肌细胞电生理效应的研究和报道较少。本研究旨在通过应用细胞内微电极技术观察H2S对于缺血不同时期心肌细胞电生理效应,并探讨其可能的作用机制。
目的:旨在观察H2S对缺血豚鼠乳头肌的电生理效应。
方法:1.利用细胞内玻璃微电极技术,记录模拟缺血环境中豚鼠乳头状肌细胞的放电。使用我研究室自行设计的心脏细胞跨膜动作电位采样、处理系统对细胞动作电位各参数进行采集、记录和分析。2.利用透射电镜技术观察各处理组模拟缺血环境下心肌细胞超微形态学变化,进一步证明电生理改变的结构基础。
结果:1.( 1 ). H2S前处理可浓度依赖性地( 50μmol/L、100μmol/L、200μmol/L )使乳头状肌细胞动作电位的平台期( PPD )、复极化50%时间( APD50 )、复极化90%时间( APD90 )、动作电位时程( APD )以及零相最大上升速度( Vmax )在各缺血时间点( 5 min、10 min、15 min、20 min、25 min、30 min )与单纯缺血组有显著性差异。在缺血早期H2S可加速PPD、APD50、APD90、APD和Vmax的减小,缺血后期H2S相反促进了PPD、APD50、APD90、APD和Vmax恢复。( 2 ).缺血预适应对缺血乳头状肌细胞电生理参数( PPD、APD50、APD90、APD及Vmax )的影响和H2S前处理效应相似。( 3 ).应用KATP通道阻断剂格列苯脲( Gli; 20μmol/L ),可部分阻断H2S对乳头状肌细胞的电生理效应。( 4 ).胱硫醚-γ-裂解酶( cystathionine-γ-lyase, CSE )的不可逆抑制剂DL-propargylglycine( PPG; 200μmol/L ),可抑制缺血早期电生理参数( PPD、APD50、APD90、APD及Vmax )的减小,并使得缺血晚期上述参数的改善恶化。2. ( 1 ).正常豚鼠乳头状肌细胞在透射电镜下显示肌节排列整齐,细胞核周线粒体和糖原颗粒含量非常丰富,且线粒体嵴和膜清晰可见。( 2 ).乳头状肌细胞给予模拟缺血液后,电镜显示肌节排列紊乱,部分肌浆网扩张,细胞质有水肿,糖原颗粒数量减少,线粒体部分嵴和膜融合不清或缺失。( 3 ).缺血乳头状肌细胞在给予缺血预适应或给予H2S前处理后,其超微形态结构的改变均不同程度减轻。( 4 ).格列苯脲前处理后,H2S保护缺血乳头状肌细胞形态学损伤的作用减轻。( 5 ). PPG前处理后,乳头状肌细胞缺血后电镜显示,乳头肌明显水肿,肌节排列紊乱,肌节有阻断或消失,线粒体和糖原颗粒数量明显下降,线粒体大部分嵴和膜融合不清或缺失(空泡化)。
结论:外源性H2S前处理可能通过兴奋KATP通道促进缺血早期K+外流,并且由于对Na+-K+-ATP酶的保护作用改善了缺血晚期对K+的重摄取,进而影响缺血环境下豚鼠乳头状肌细胞的电生理效应;乳头状肌细胞内源性产生的H2S可能在心肌缺血损伤时发挥着重要的电生理作用。透射电镜下观察发现外源性H2S可减轻乳头状肌细胞缺血损伤时的微形态学改变。而阻断内源性H2S后,可加重心室乳头状肌细胞在缺血时超微结构的损伤。
Hydrogen sulfide (H2S) has been proved to be the third endogenous signaling gasotransmitter, besides nitric oxide (NO) and carbon monoxide (CO), and shows the important physiological functions. Endogenous H2S can be generated from L-cysteine catalyzed by two pyridoxal-5′-phosphate-dependent enzymes, cystathionie-β-synthase (CBS) and cystathionine-γ-lyase (CSE). H2S is directly produced in myocardial tissues, arterial and venous tissues by CSE. It is now clear that H2S has the vasorelaxtant functions. In vascular smooth muscle cells (VSMCs), the opening of ATP-sensitive potassium channels (KATP channels) and the entrance of extracellular calcium were reported to be involved in H2S actions. KATP channels widely distribute in heart cells. It is known that the opening of KATP channels in myocardium is an important endogenous cardioprotective mechanism. Recently, H2S has been found to play a negative inotropic role in the heart and could be endogenously produced by the cardiac tissues as a physiological cardiac function regulator, which is mediated by KATP channel pathway. In the normal papillary muscles exogenous H2S can decrease the duration of action potential (APD) in a concentration-dependent manner, And in partially depolarized papillary muscles H2S can also decrease the amplitude of action potential (APA), overshoot (OS) and maximal velocity of depolarization at 0 (Vmax) beside the APD. Though the cardioprotection of H2S on ischemia heart had been reported, the electrophysiological effects of H2S on ischemic cardiomyocytes were not clear. The purpose of this study is to investigate the effects of H2S on electrophysiology of ischemic cardiomycytes and its underlying mechanisms by using intracellular microelectrode technique.
Aim: To study the electrophysiological effects of hydrogen sulfide (H2S) on ischemic guinea pig papillary muscles. Methods: 1. Parameters of action potentials (APs) of the ischemic guinea pig papillary muscles were recorded using intracellular microelectrodes and analyzed with the system of sampling and processing cardiac transmembrane potential designed by our department. 2. The ultrastructure of papillary muscle cells observed by transmission electron microscope to prove the electrophysiological’s changes of structure background due to different treatments.
Results: 1.(1). H2S pretreatment (50μmol/L、100μmol/L、200μmol/L) changed the plateau period duration (PPD), duration of action potential (APD), 50% of APD (APD50), 90% APD(APD90), and maximal rate of depolarization at phase 0 (Vmax) of ischemic guinea pig papillary muscles in a concentration-dependent manner. H2S pretreatment promoted shortening of APD, APD50, APD90, PPD and Vmax at the early phase of ischemia, and improving of APD, APD50, APD90, PPD and Vmax at the late phase of ischemia, there is a significant changment compaired with ischemia. (2). The parameters of PPD、APD50、APD90、APD and Vmax had similar changes reduced by exogenous H2S pretreatment after ischemic preconditioning. (3). Pretreatment with KATP channel blocker glibenclamide (Gli; 20μmol/L) could partially block the effects of H2S pretreatment (100μmol/L). (4). The shortening of parameters PPD、APD50、APD90、APD and Vmax were weakened at the early phase of ischemia and the improving of these parameters were decreased at the late phase of ischemia by DL-propargylglycine (PPG, an inreversible inhibitor of CSE; 200μmol/L). 2. (1). The ultrastructure of normal guinea pig papillary muscle cell showing the sarcomere and light dark band were clear, mitochondria and glycogenosome were abundant, and mitochondrial cristae and membrane were clear. (2). The TEM showing the sarcomere was in a bad apposition, Sarcoplasmic reticulum dilated, cytoplasmic was edema, glycogenosome decreased, mitochondrial cristae and membrane were anastomosis or absence. (3). The damage of ultrastructure given ischemia insult relieved by ischemic preconditioning or H2S pretreatment. (4). Glibenclamide could block the protect effect of papillary muscle ultrastructure due to H2S pretreatment. (5). The ultrastructure’s observation of the ischemic papillary muscle cell after PPG preteatment. Papillary muscle was severe edema; sarcomeres were in bad arrangement, containing breakage or abolition. The quantity of mitochondria and glycogenosome decreased significantly. Mitochondria cristae and membrane in a great measure were anastomosis or vacuolization.
Conclusion: All these results suggest that effects of H2S on papillary muscles are due to an increase in potassium efflux through opening the KATP channels at the early phase of ischemia, and acceleration in potassium reuptake through improving the Na+-K+-ATPase at the late phase of ischemia. Endogenous H2S may act as important regulator in electrophysiological characters in ischemic papillary muscles. The observation of papillary muscle cell’s ultrastructure showed that exogenous H2S could decrease the damage of ischemic guinea pig papillary muscles. The absence of endogenous H2S could aggravate the damage of papillary muscle cell’s ultrastructure when the papillary muscle insulted ischemia.
目的:旨在观察H2S对缺血豚鼠乳头肌的电生理效应。
方法:1.利用细胞内玻璃微电极技术,记录模拟缺血环境中豚鼠乳头状肌细胞的放电。使用我研究室自行设计的心脏细胞跨膜动作电位采样、处理系统对细胞动作电位各参数进行采集、记录和分析。2.利用透射电镜技术观察各处理组模拟缺血环境下心肌细胞超微形态学变化,进一步证明电生理改变的结构基础。
结果:1.( 1 ). H2S前处理可浓度依赖性地( 50μmol/L、100μmol/L、200μmol/L )使乳头状肌细胞动作电位的平台期( PPD )、复极化50%时间( APD50 )、复极化90%时间( APD90 )、动作电位时程( APD )以及零相最大上升速度( Vmax )在各缺血时间点( 5 min、10 min、15 min、20 min、25 min、30 min )与单纯缺血组有显著性差异。在缺血早期H2S可加速PPD、APD50、APD90、APD和Vmax的减小,缺血后期H2S相反促进了PPD、APD50、APD90、APD和Vmax恢复。( 2 ).缺血预适应对缺血乳头状肌细胞电生理参数( PPD、APD50、APD90、APD及Vmax )的影响和H2S前处理效应相似。( 3 ).应用KATP通道阻断剂格列苯脲( Gli; 20μmol/L ),可部分阻断H2S对乳头状肌细胞的电生理效应。( 4 ).胱硫醚-γ-裂解酶( cystathionine-γ-lyase, CSE )的不可逆抑制剂DL-propargylglycine( PPG; 200μmol/L ),可抑制缺血早期电生理参数( PPD、APD50、APD90、APD及Vmax )的减小,并使得缺血晚期上述参数的改善恶化。2. ( 1 ).正常豚鼠乳头状肌细胞在透射电镜下显示肌节排列整齐,细胞核周线粒体和糖原颗粒含量非常丰富,且线粒体嵴和膜清晰可见。( 2 ).乳头状肌细胞给予模拟缺血液后,电镜显示肌节排列紊乱,部分肌浆网扩张,细胞质有水肿,糖原颗粒数量减少,线粒体部分嵴和膜融合不清或缺失。( 3 ).缺血乳头状肌细胞在给予缺血预适应或给予H2S前处理后,其超微形态结构的改变均不同程度减轻。( 4 ).格列苯脲前处理后,H2S保护缺血乳头状肌细胞形态学损伤的作用减轻。( 5 ). PPG前处理后,乳头状肌细胞缺血后电镜显示,乳头肌明显水肿,肌节排列紊乱,肌节有阻断或消失,线粒体和糖原颗粒数量明显下降,线粒体大部分嵴和膜融合不清或缺失(空泡化)。
结论:外源性H2S前处理可能通过兴奋KATP通道促进缺血早期K+外流,并且由于对Na+-K+-ATP酶的保护作用改善了缺血晚期对K+的重摄取,进而影响缺血环境下豚鼠乳头状肌细胞的电生理效应;乳头状肌细胞内源性产生的H2S可能在心肌缺血损伤时发挥着重要的电生理作用。透射电镜下观察发现外源性H2S可减轻乳头状肌细胞缺血损伤时的微形态学改变。而阻断内源性H2S后,可加重心室乳头状肌细胞在缺血时超微结构的损伤。
Hydrogen sulfide (H2S) has been proved to be the third endogenous signaling gasotransmitter, besides nitric oxide (NO) and carbon monoxide (CO), and shows the important physiological functions. Endogenous H2S can be generated from L-cysteine catalyzed by two pyridoxal-5′-phosphate-dependent enzymes, cystathionie-β-synthase (CBS) and cystathionine-γ-lyase (CSE). H2S is directly produced in myocardial tissues, arterial and venous tissues by CSE. It is now clear that H2S has the vasorelaxtant functions. In vascular smooth muscle cells (VSMCs), the opening of ATP-sensitive potassium channels (KATP channels) and the entrance of extracellular calcium were reported to be involved in H2S actions. KATP channels widely distribute in heart cells. It is known that the opening of KATP channels in myocardium is an important endogenous cardioprotective mechanism. Recently, H2S has been found to play a negative inotropic role in the heart and could be endogenously produced by the cardiac tissues as a physiological cardiac function regulator, which is mediated by KATP channel pathway. In the normal papillary muscles exogenous H2S can decrease the duration of action potential (APD) in a concentration-dependent manner, And in partially depolarized papillary muscles H2S can also decrease the amplitude of action potential (APA), overshoot (OS) and maximal velocity of depolarization at 0 (Vmax) beside the APD. Though the cardioprotection of H2S on ischemia heart had been reported, the electrophysiological effects of H2S on ischemic cardiomyocytes were not clear. The purpose of this study is to investigate the effects of H2S on electrophysiology of ischemic cardiomycytes and its underlying mechanisms by using intracellular microelectrode technique.
Aim: To study the electrophysiological effects of hydrogen sulfide (H2S) on ischemic guinea pig papillary muscles. Methods: 1. Parameters of action potentials (APs) of the ischemic guinea pig papillary muscles were recorded using intracellular microelectrodes and analyzed with the system of sampling and processing cardiac transmembrane potential designed by our department. 2. The ultrastructure of papillary muscle cells observed by transmission electron microscope to prove the electrophysiological’s changes of structure background due to different treatments.
Results: 1.(1). H2S pretreatment (50μmol/L、100μmol/L、200μmol/L) changed the plateau period duration (PPD), duration of action potential (APD), 50% of APD (APD50), 90% APD(APD90), and maximal rate of depolarization at phase 0 (Vmax) of ischemic guinea pig papillary muscles in a concentration-dependent manner. H2S pretreatment promoted shortening of APD, APD50, APD90, PPD and Vmax at the early phase of ischemia, and improving of APD, APD50, APD90, PPD and Vmax at the late phase of ischemia, there is a significant changment compaired with ischemia. (2). The parameters of PPD、APD50、APD90、APD and Vmax had similar changes reduced by exogenous H2S pretreatment after ischemic preconditioning. (3). Pretreatment with KATP channel blocker glibenclamide (Gli; 20μmol/L) could partially block the effects of H2S pretreatment (100μmol/L). (4). The shortening of parameters PPD、APD50、APD90、APD and Vmax were weakened at the early phase of ischemia and the improving of these parameters were decreased at the late phase of ischemia by DL-propargylglycine (PPG, an inreversible inhibitor of CSE; 200μmol/L). 2. (1). The ultrastructure of normal guinea pig papillary muscle cell showing the sarcomere and light dark band were clear, mitochondria and glycogenosome were abundant, and mitochondrial cristae and membrane were clear. (2). The TEM showing the sarcomere was in a bad apposition, Sarcoplasmic reticulum dilated, cytoplasmic was edema, glycogenosome decreased, mitochondrial cristae and membrane were anastomosis or absence. (3). The damage of ultrastructure given ischemia insult relieved by ischemic preconditioning or H2S pretreatment. (4). Glibenclamide could block the protect effect of papillary muscle ultrastructure due to H2S pretreatment. (5). The ultrastructure’s observation of the ischemic papillary muscle cell after PPG preteatment. Papillary muscle was severe edema; sarcomeres were in bad arrangement, containing breakage or abolition. The quantity of mitochondria and glycogenosome decreased significantly. Mitochondria cristae and membrane in a great measure were anastomosis or vacuolization.
Conclusion: All these results suggest that effects of H2S on papillary muscles are due to an increase in potassium efflux through opening the KATP channels at the early phase of ischemia, and acceleration in potassium reuptake through improving the Na+-K+-ATPase at the late phase of ischemia. Endogenous H2S may act as important regulator in electrophysiological characters in ischemic papillary muscles. The observation of papillary muscle cell’s ultrastructure showed that exogenous H2S could decrease the damage of ischemic guinea pig papillary muscles. The absence of endogenous H2S could aggravate the damage of papillary muscle cell’s ultrastructure when the papillary muscle insulted ischemia.
引文
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1 Hosoki R, Matsuki N, kimura H. The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide. Biochem Biophys Res Commum, 1997, 273(3): 527-531.
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3 Zhao WM, Zhang J, Lu YJ, et al. The vasorelaxant effect ofH2S as a novel endogenous gaseous KATP channel opener. EMBO J, 2001, 20(21): 6008-6016.
4 Stipanuk MH, Beck PW. Characterization of the enzymatic capacity for cysteine desulphhydration in liver and kidney of the rat. Biochem J, 1982, 206(2): 267 - 277.
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8 Zhao WM, Joseph FN, Wang R. Modulation of endogenous production of H2S in rat tissues. Canadian Journal of Physiology and Pharmacology, 2003, 81(9): 848-853.
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12 Geng B, Yang JH, Oi YF, et al. H2S generated by heart in rat and its effects on cardiac function. Biochem Biophys Res Commun, 2004, 313(2): 362-368
13 Xu M, Wu YM, et al. Electrophysiological effects of hydrogen sulfide on guinea pig papillary muscles in vitro. Acta Physiologica Sinica, April 25, 2007, 59(2): 215-220
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16 Marte Bliks?en, Mari-Liis Kaljusto, et al. Effects of hydrogen sulphide on ischaemia—reperfusion injury and ischaemic preconditioning in the isolated, perfused rat heart. European Journal of Cardio-thoracic Surgery, 2008, 34(2): 344-349
17 Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation, 1986, 74:1124-1136
18 Eisen A, Fisman EZ, Rubenfire M, et al. Ischemic preconditioning: nearly two decades of research: a comprehensive review. Atherosclerosis, 2004, 172:201-210
19 Bian JS, Yong QC, Pan TT, et al. Role of Hydrogen Sulfidein the Cardioprotection Caused by Ischemic Preconditioning in the Rat Heart and Cardiac Myocytes. Journal of Pharmacology And Experimental Therapeutics, 2006, 316:670-678
20 Johansen D, Ytrehus K, Baxter GF. Exogenous hydrogen sulfide (H2S) protectsagainst regional myocardial ischemia-reperfusion injury—evidence for a role of KATP channels. Basic Res Cardiol, 2006, 101:53-60
21 Tang G, Wu L, Liang W, Wang R. Direct stimulation of K(ATP) channels by exogenous and endogenous hydrogen sulfide in vascular smooth muscle cells. Mol Pharmacol, 2005, 68:1757–1764.
22 Hu LF, Pan TT, Bian JS, et al. Cyclooxygenase-2 mediates the delayed cardioprotection induced by hydrogen sulfide preconditioning in isolated rat cardiomyocytes. Pflugers Arch-Eur J Physiol, 2008, 455:971–978
23 Pan TT, Kay Li Neo, Hu LF, et al. H2S preconditioning-induced PKC activation regulates intracellular calcium handling in rat cardiomyocytes. Am J Physiol Cell Physiol, 2008, 294:169-177
24陈晓波,杜军保,耿彬,等.硫化氢对培养的大鼠主动脉平滑肌细胞增殖的抑制作用.中国病理生理杂志, 2003, 19:1009-1011.
25陈晓波,杜军保,张春雨,等.硫化氢对低氧性肺动脉高压大鼠肺动脉增殖细胞核抗原Bcl-2的调节作用.实用儿科临床杂志, 2004:185-187
26 Yang G, Sun X, Wang R. Hydrogen sulfide-induced apoptosis of human aorta smooth muscle cells via the activation of mitogen- activated protein kinases and caspase-3. FASEB J, 2004,18: 1782-1784
27 Saima Muzaffar, Nilima Shukla, Mark Bond. et al. Exogenous Hydrogen Sulfide Inhibits Superoxide Formation, NOX-1 Expression and Rac1 Acticity in Human Vascular Smooth Muscle Cells. Vascular Research, 2008, 45:521-528
28 Ling L, Matthew W, Yan YG. et al. Characterization of a novel, water-soluble Hydrogen sulfide-releasing molecule(GYY4137) new insights into the Biology of Hydrogen sulfide. Circulation, 2008, 117:2351-2360
29 Dawe GS, Han SP, Bian JS. et al. Hydrogen sulphide in the hypothalamus causes an ATP-sensitive K+ channel-dependent decrease in blood pressure in freely moving rats. Neuroscience, 2008, 152(1):169-177
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1 Hosoki R, Matsuki N, kimura H. The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide. Biochem Biophys Res Commum, 1997, 273(3): 527-531.
2 Wang R. Two’s company, three’s a crowd: Can H2S be the third endogenous gaseous transmitter? FASEB J, 2002, 16(13): 1792- 1798.
3 Zhao WM, Zhang J, Lu YJ, et al. The vasorelaxant effect ofH2S as a novel endogenous gaseous KATP channel opener. EMBO J, 2001, 20(21): 6008-6016.
4 Stipanuk MH, Beck PW. Characterization of the enzymatic capacity for cysteine desulphhydration in liver and kidney of the rat. Biochem J, 1982, 206(2): 267 - 277.
5 Ewelina lowicka, Jerzy Beltowski. Hydrogen sulfide (H2S)-the third gas of interest for pharmacologists. Pharmacological Reports, 2007, 59, 4-24.
6 Furne J, Springfield J, Koenig T, et al. Oxidation of hydrogen sulfide and methanethiol to thiosulfate by rat tissues:a specialized function of the colonic mucosa. Biochem pharmacol, 2001, 62(2): 255-259.
7 Cheng YQ, Joseph FN, Tang GH, et al. Hydrogen sulfide induced relaxation of resistance mesenteric artery beds of rats. Heart Circ Physiol, 2004, 287(5): H2316-H2323.
8 Zhao WM, Joseph FN, Wang R. Modulation of endogenous production of H2S in rat tissues. Canadian Journal of Physiology and Pharmacology, 2003, 81(9): 848-853.
9张清友,杜军保,张春雨,等.内源性一氧化氮对低氧大鼠肺动脉硫化氢胱硫醚2γ2裂解酶体系的影响.实用儿科临床杂志, 2003 ,18 (11) :865-867
10 Zhang Q, Du J, Zhang W. Impact of hydrogen sulfide on carbon monoxide/heme oxygenase pathway in the pathogen esis of hypoxic pulmonary hypertention. Biochem Bio phys ResCommun, 2004, 317(1): 30 - 37.
11耿彬,杨靖辉,唐朝枢,等.硫化氢对大鼠离体灌流心脏心功能的影响.中国病理生理杂志, 2005, 21(1): 1-5.
12 Geng B, Yang JH, Oi YF, et al. H2S generated by heart in rat and its effects on cardiac function. Biochem Biophys Res Commun, 2004, 313(2): 362-368
13 Xu M, Wu YM, et al. Electrophysiological effects of hydrogen sulfide on guinea pig papillary muscles in vitro. Acta Physiologica Sinica, April 25, 2007, 59(2): 215-220
14 Geng B, Chang L, Pan CS, et al. Endogenous hydrogen sulfide regulation of myocardial injury induced by isoproterenol. Biochem Biophys Res Commun, 2004, 318: 756-763
15 Zhu YZ, Wang ZJ, Ho P, et al. Hydrogen sulfide and its possible roles in myocardial ischemia in experimental rats. J Appl Physiol, 2007, 102:261-268
16 Marte Bliks?en, Mari-Liis Kaljusto, et al. Effects of hydrogen sulphide on ischaemia—reperfusion injury and ischaemic preconditioning in the isolated, perfused rat heart. European Journal of Cardio-thoracic Surgery, 2008, 34(2): 344-349
17 Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation, 1986, 74:1124-1136
18 Eisen A, Fisman EZ, Rubenfire M, et al. Ischemic preconditioning: nearly two decades of research: a comprehensive review. Atherosclerosis, 2004, 172:201-210
19 Bian JS, Yong QC, Pan TT, et al. Role of Hydrogen Sulfidein the Cardioprotection Caused by Ischemic Preconditioning in the Rat Heart and Cardiac Myocytes. Journal of Pharmacology And Experimental Therapeutics, 2006, 316:670-678
20 Johansen D, Ytrehus K, Baxter GF. Exogenous hydrogen sulfide (H2S) protectsagainst regional myocardial ischemia-reperfusion injury—evidence for a role of KATP channels. Basic Res Cardiol, 2006, 101:53-60
21 Tang G, Wu L, Liang W, Wang R. Direct stimulation of K(ATP) channels by exogenous and endogenous hydrogen sulfide in vascular smooth muscle cells. Mol Pharmacol, 2005, 68:1757–1764.
22 Hu LF, Pan TT, Bian JS, et al. Cyclooxygenase-2 mediates the delayed cardioprotection induced by hydrogen sulfide preconditioning in isolated rat cardiomyocytes. Pflugers Arch-Eur J Physiol, 2008, 455:971–978
23 Pan TT, Kay Li Neo, Hu LF, et al. H2S preconditioning-induced PKC activation regulates intracellular calcium handling in rat cardiomyocytes. Am J Physiol Cell Physiol, 2008, 294:169-177
24陈晓波,杜军保,耿彬,等.硫化氢对培养的大鼠主动脉平滑肌细胞增殖的抑制作用.中国病理生理杂志, 2003, 19:1009-1011.
25陈晓波,杜军保,张春雨,等.硫化氢对低氧性肺动脉高压大鼠肺动脉增殖细胞核抗原Bcl-2的调节作用.实用儿科临床杂志, 2004:185-187
26 Yang G, Sun X, Wang R. Hydrogen sulfide-induced apoptosis of human aorta smooth muscle cells via the activation of mitogen- activated protein kinases and caspase-3. FASEB J, 2004,18: 1782-1784
27 Saima Muzaffar, Nilima Shukla, Mark Bond. et al. Exogenous Hydrogen Sulfide Inhibits Superoxide Formation, NOX-1 Expression and Rac1 Acticity in Human Vascular Smooth Muscle Cells. Vascular Research, 2008, 45:521-528
28 Ling L, Matthew W, Yan YG. et al. Characterization of a novel, water-soluble Hydrogen sulfide-releasing molecule(GYY4137) new insights into the Biology of Hydrogen sulfide. Circulation, 2008, 117:2351-2360
29 Dawe GS, Han SP, Bian JS. et al. Hydrogen sulphide in the hypothalamus causes an ATP-sensitive K+ channel-dependent decrease in blood pressure in freely moving rats. Neuroscience, 2008, 152(1):169-177