摘要
心肌缺血再灌注损伤(myocardial ischemia reperfusion injury,MIRI)的发生和发展过程是一个多因素相互作用的级联反应,主要的损伤机制有自由基损伤、钙超载、微血管损伤和白细胞的作用等。近年来研究发现,补体、选择素、内皮素和细胞凋亡等均参与了MIRI的病理变化过程。可见,MIRI可能是多分子、多机制、相互影响、相互促进的病理变化。至今MIRI一直是心肌缺血治疗中难以解决的问题。
我国中药资源丰富,从中寻找防治MIRI的安全有效药物,特别是对其活性成分进行药效学及作用机制的研究,对于开发我国丰富的中药资源和促进中药现代化具有重要意义。
多年来,本课题组一直致力于发掘广西丰富的民族草药资源,筛查副作用小、疗效较好的广西民族草药/活性部位。我们前期开展了大量的基础研究工作,阶段性实验发现:(1)从玉郎伞分离得到的玉郎伞黄酮(YLSF)预处理能明显降低MIRI大鼠血浆中AST、LDH、LDH1和MDA含量,能提高SOD活性,降低心肌梗死范围。提示,YLSF对大鼠心肌MIRI具有显著的保护作用。此外,两种YLS单体对体外培养大鼠乳鼠心肌细胞缺氧/复氧损伤具有保护作用,其机制可能与清除自由基、抑制心肌细胞Ca2+超载有关;进一步研究还发现,YLS两种黄酮单体尚具有抗氧化、耐缺氧、抗凝血以及有较强的清除自由基的作用。
(2)从柿叶提取得到的PLF可显著改善MIRI所致的大鼠离休心功能损伤,减少CK、CK-MB、LDH、LDH1的释放和心肌组织MDA的产生,增加SOD、Na+-K+-ATP酶和Ca2+-ATP酶的活性,说明,PLF对大鼠MIRI具有保护作用,其机制可能与提高SOD活性、抗氧自由基、减少脂质过氧化反应有关。而研究PLF对血压的影响,发现PLF对正常大鼠和L-NAME诱导的高血压大鼠的血压和心率均有降低作用。另一研究证明,PLF可能是通过增加内源性舒血管活性物质的释放和减少内源性收缩血管活性物质的释放来调节两者之间的平衡而发挥其抗高血压作用。总之,前期研究表明,YLSF和PLF对大鼠MIRI具有明显的保护作用,
其作用机制与抗氧化、清除氧自由基等多个环节有关。为了更进一步地了解YLSF和PLF对大动物(猴、犬)MIRI的影响,完善其临床前研究,我们分别用猴和犬MIRI模型,研究YLSF和PLF对MIRI的保护作用,研究分两部分:
第一部分:玉郎伞黄酮对猴心肌缺血再灌注损伤的保护作用及机制研究
目的:研究玉郎伞黄酮(YLSF)对猴心肌缺血再灌注损伤(MIRI)的保护作用及其机制。
方法:将实验猴随机分为5组,每组4只:假手术(SHAM)组、心肌缺血再灌注损伤(MIRI)模型组、YLS黄酮低剂量组(YLSFL)组、YLS黄酮高剂量(YLSFH)组、地尔硫卓阳性药(DIL)组。缺血前30min经十二指肠注射给药。结扎冠状动脉左前降支60min后,再灌注180min,建立MIRI模型。再灌注结束后测定下列各项指标:(1)利用MPA心功能分析系统观察并纪录在急性缺血和再灌注状态下血流动力学指标(HR、LVSP、Lvedp、+dp/dtmax、-dp/dtmax)的变化。(2)取缺血区的心肌组织,常规制作组织切片、电镜切片,光镜、电镜下观察心肌组织病理结构和超微结构的变化并拍照。(3)从股静脉脉采血,离心,取上层血清,测定AST、LDH、LDH1、CK、CK-MB、SOD、GSH-Px、TNOS、MDA和NEFA;取缺血区心肌组织,按试剂盒说明测定Na+K+-ATPase和Ca2+Mg2+-ATPase活性。(4)取缺血区心肌组织,测定心肌组织凋亡相关蛋白Bcl-2和Bax表达、核因子-κB表达、心肌细胞凋亡、心肌ANT1、Caspase-3 mRNA表达。
结果:(1)YLSF对心脏血流动力学的影响:与模型组比较,YLSFH、YLSFL组在再灌注180min时对LVSP、+dp/dtmax有明显的提高作用,而对HR、LVDEP和-dp/dtmax的作用不明显。(2)YLSF对血液生化学指标的影响:YLSF能明显下调各心肌酶、MDA和NEFA含量;提高SOD、GSH-Px、Na+K+-ATPase和Ca2+Mg2+-ATPase活性。(3)YLSF对心肌组织形态学的影响:从组织病理学角度上看,与模型组比较,YLSF给药组心肌受损程度明显减轻。(4)YLSF对相关蛋白Bcl-2和Bax表达、核因子-κB表达的影响:YLSFH、YLSFL组均能明显降低心肌Bax蛋白表达,能显著增加Bcl-2/Bax的比率。YLSFH能明显增加Bcl-2蛋白表达,而YLSFL则对Bcl-2蛋白表达无影响。YLSF给药组NF-κBp65表达降低,阳性细胞百分率下降。(5)YLSF对心肌细胞凋亡的影响:YLSFH组可减轻心肌细胞凋亡程度。(6)YLSF对心肌ANT1、Caspase-3 mRNA表达的影响:与MIRI组比较,YLSFH组、YLSFL组ANT1mRNA表达上调(P<0.05),YLSH组Caspase3的mRNA表达下调(P<0.05)。(7)YLSF对心肌细胞超微结构的影响: YLSF能明显减轻心肌超微结构的破坏。
结论:YLSF对猴MIRI具有显著的保护作用,其机制可能与改善心功能、抗脂质过氧化损伤、下调Bax蛋白表达、增加Bcl-2/Bax的比率,下调NF-κBp65表达,减轻心肌细胞凋亡程度,以及上调ANT1mRNA的表达以及通过下调Caspase3 mRNA的表达有关。
第二部分:柿叶黄酮对犬心肌缺血再灌注损伤的保护作用及机制研究
目的:研究柿叶黄酮(PLF)对犬心肌缺血再灌注损伤(MIRI)的保护作用并对其机制进行初步探讨。
方法:选取实验用比格犬随机分为5组,每组6只:假手术组、心肌缺血再灌注损伤(MIRI)组、柿叶黄酮低剂量(PLFL)组、柿叶黄酮高剂量(PLFH)组、地尔硫卓(DIL)组。缺血前30min经十二指肠注射给药。结扎冠状动脉左前降支60min后,再灌注180min,建立MIRI模型。再灌注结束后测定下列各项指标:(1)利用MPA心功能分析系统观察并纪录在急性缺血和再灌注状态下血流动力学指标(HR、LVSP、Lvedp、+dp/dtmax、-dp/dtmax、IT、ET、IT/ET)的变化。(2)取缺血区的心肌组织,常规制作组织切片、电镜切片,光镜、电镜下观察心肌组织病理结构和超微结构的变化并拍照。(3)从股静脉脉采血,离心,取上层血清,按试剂盒说明测定AST、CK、CK-MB、LDH、LDH1,SOD、GSH-Px和TNOS的活性、MDA和NEFA含量;取缺血区心肌组织,按试剂盒说明测定AST、CK、CK-MB、LDH、LDH1,SOD、GSH-Px、TNOS、ATP酶的活性、MDA和NEFA含量。(4)取缺血区心肌组织,免疫组化法测定Bcl-2和Bax蛋白表达。
结果:(1)与MIRI组相比,在再灌注180min(r180min)时,PLFH组HR、LVSP、+dp/dtmax、ET显著高于MIRI组(P<0.01或P<0.05),而Lvedp、-dp/dtmax、IT、IT/ET显著低于MIRI组(P<0.01或P<0.05)。(2)光镜下观察,MIRI组心肌纤维排列紊乱、肿胀、部分断裂,甚至出现片状坏死,周围有炎性细胞浸润,红细胞漏出明显。PLFL、PLFH组的损伤明显减轻。电镜下观察,MIRI组的心肌细胞的肌丝、线粒体、闰盘等破坏明显,而PLFL、PLFH组则明显减轻。(3)与MIRI组比较,PLF能显著抑制血清中心肌酶活性和MDA、NEFA含量的提高,抑制血清中SOD、GSH-Px、TNOS活性的降低(P<0.01或P<0.05);PLF还能同时降低组织中MDA和NEFA含量,提高心肌酶、SOD、GSH-Px和ATP酶的活性(P<0.01或P<0.05)。(4)与MIRI组比较, PLFL、PLFH组Bcl-2蛋白表达明显增高(P<0.01或P<0.05),而NF-κBp65、Bax蛋白表达及Bax/Bcl-2的比值明显降低(P<0.01或P<0.05)。
结论:柿PLF对MIRI具有明显的保护作用。其抑制可能与抗脂质过氧化损伤、保护ATP酶活性、降低NEFA含量、提高TNOS活性、改善心功能和抑制心肌细胞凋亡有关。
The occurance and development of myocardial ischemia reperfusion injury (MIRI) are multiple cascade associated with various factors, for example, free radical injury, calcium overload, microvascular injury and the effects of leucocytes. The most recent researches indicate that comlements, selectins, endothelin and apoptosis are involved in the pathophysiological process of MIRI. Obviously MIRI is a complex pathological process which multiple factors interact and improve each other. MIRI is a troublesome problem of mycardial ischemia for long time.
The natural resources of Chinese medicinal materials is very rich in China. It is of great significance to search for the safe and effective herbs for the prevention and treatment of MIRI, particularly for the active components in these herbs and the study of their pharmacodynamics and mechanisms on anti-MIRI, which can help to develop our country’s herbal resources and to make the modernization of Traditional Chinese Medicine.
For the last more than ten years, we have gone in for exploring the rich ethnic herbal resources in Guangxi. After screening a large number of herbs, two better effective anti-MIRI active site of the ethnic medical herbs—Yulangsan flavonoids (YLSF) and persimmon leaf flavonoids (PLF) were found. Our preliminary studies showed that: (1) YLSF preconditioning could significantly decrease the activitis of AST, LDH and LDH1, the contents of MDA, and the myocardial infarct size, and increase the activity of SOD. The results indicated that YLSF had a significant protective effect on myocardial ischemia reperfusion injury (MIRI) in rats. In addition, the two flavone morphons had good effects on hypoxia/reoxygenation injury in cultured neonatal rat cardiomyocytes, which was related with scavenging free radicals and inhibiting Ca2+-overloading. The further study showed that the two flavone morphons also had better antioxidation, anti-hypoxia,anticoagulation, and scavenging of free radicals.
(2) PLF could obviously recover cardiac function, reduce the releases of CK, CK-MB, LDH, and LDH-1 from rat hearts of MIRI, increase the activities of SOD, Na+-K+-ATPase and Ca2+-ATPase, and decrease the MDA product. It were suggested that PLF may offer myocardial protective effect against MIRI,the mechanism might be related to attenuating free radicals. Other, the study of antihypertensive effect of PLF showed that PLF could decrease blood pressur and heart rat in normal rats and L-NAME induced hypertention in rats, and might adjust the imbalance of cardiovascular active substances by increasing the release of endogenous vasodilators and reducing the release of endogenous vasoconstrictors, resulting in antihypertention.
In short, our prior studies indicated that YLSF and PLF had significant protective effects on MIRI in rats, which are related with many kinds of factors,such as antioxidation and scavenging free radicals. To understand further the influence of YLSF and PLF on MIRI in big animal (rhesus monkeys or dogs), and to accomplish their pre-clinical studies, the rhesus monkey or dog model was used to research the effects of YLSF and PLF on MIRI. The experiments contained two parts as the following:
Part I Effect and action mechanism of Yulangsan flavonoids on myocardial ischemic reperfusion in rhesus monkeys
Objective: To study the effect and action mechanism of Yulangsan flavonoids (YLSF) on myocardial ischemic reperfusion injury (MIRI) in rhesus monkeys.
Methods: Rhesus monkeys were randomly divided into 5 groups: sham operation (SHAM) group, myocardial ischemia reperfusion injury (MIRI) group, YLSF low dose (YLSFL) group, YLSF high dose(YLSFH) group, Diltiazem(DIL) group, and there were 4 animals at each group. Different doses of drug were administered into duodenum 30 min before ligation of the left anterior descending coronary artery (LAD) for 60 min and followed with reperfusion for 180 min to establish MIRI model. Determination of the following indexes: (1) MPA-cardiac function acquisition and analytical system (MPA-CFS) was used to record HR, LVSP, Lvedp, +dp/dtmax, and -dp/dtmax. (2) Myocardial ischemic tissues were taken to make histological section and electron microscopic section S.A. for observing the changes of histopathology and ultrastructure of myocardium under optical microscope or transmission electron microscope respectively, and taking the pictures with camera simultaneously. (3) The blood was collected via the femoral vein, centrifuged, and the upper serum was taken for detecting activities of AST, LDH, LDH1, CK, CK-MB, SOD, GSH-Px, TNOS, MDA and NEFA in each Beagle dog. The myocardial ischemic tissues were taken for determining the activities of ATPase. (4) The myocardial ischemic tissues were taken for determining Bcl-2, Bax and NF-κB protein expressions, cardiac muscle cell apoptosis, ANT1 and Caspase 3 mRNA expressions.
Results: (1). Compared with MIRI group, at 180min after reperfusion, YLSFH could significantly increased the LVSP, while could not have effect on HR, LVDEP, +dp/dtmax and -dp/dtmax。(2) Compared with MIRI group, YLSF could significantly inhibited the increasing of myocardial enzyme activity and the content of MDA and NEFA, and increase the activities of SOD, GSH-Px, Na+K+-ATPase and Ca2+Mg2+-ATPase. (3) Histopathological examination confirmed that the degree of myocardial injury in YLSF groups were obviously lessened when compared with model group. (4) The high dosage of YLSF could downregulate the expression of Bax and significantly increase the ratio of Bcl-2/Bax. The high dosage of YLSF could increase the expression of Bcl-2, but the low dosages of YLSF could not have effect on Bcl-2. YLSF could downregulate the expression of NF-κBp65 and the percentage of positive cell. (5) The high dosage of YLSF could lessen the degree of the cardiac muscle cell apoptosis. (6) Compared with MIRI group, expression of ANT1 mRNA increased in YLSFH and YLSFL, expression of Caspase 3 mRNA decreased in YLSFH significantly (P<0.05). (7) YLSF could reduce the injury of the myocardial ultrastructure.
Conclusion: Yulangsan flavonoids (YLSF) may offer myocardial protective effects against ischemia reperfusion injury, which may be related to their effects of improving hemodynamics of heart, anti-oxidation, downregulating the expression of Bax protein, increasing the Bcl-2/Bax ratio, downregulating the expression of NF-κBp65, lessening the degree of the cardiac muscle cell apoptosis, and up-regulation of ANT1 mRNA expression and down-regulation of Caspase 3 mRNA expression.
Part II The Protective Effect and Mechanisms of Persimmon leaf Flavonid on Myocardial Ischemia Reperfusion Injury in Dogs
Objective: To study the protective effect of persimmon leaf flavonoid on on myocardial ischemia reperfusion injury in dogs and its related mechanisms.
Methods: Healthy Beagle dogs were picked out and randomly divided into 4 groups with 6 dogs in each group: sham operation (SHAM) group, myocardial ischemia reperfusion injury (MIRI) group, PLF low dose (PLFL) group, PLF high (PLFH) dose group,positive drug (DIL)group. Different doses of drug were administered into duodenum 30 min before ligation of the left anterior descending coronary artery (LAD) for 60 min and followed with reperfusion for 180 min to establish MIRI model. Determine the following indexes: 1. MPA-cardiac function acquisition and analytical system (MPA-CFS) was used to record HR, LVSP, Lvedp、+dp/dtmax, -dp/dtmax, IT, ET and IT/ET. 2. Myocardial ischemic tissues were taken to make histological section and electron microscopic section S.A. for observing the changes of histopathology and ultrastructure of myocardium under optical microscope and transmission electron microscope respectively, and taking the pictures with camera simultaneously. 3.The blood was collected via the femoral vein, centrifuged, and the upper serum was taken for detecting activities of AST, CK, CK-MB, LDH, LDH1, SOD, GSH-Px and TNOS, and content of MDA and NEFA in each Beagle dog. The myocardial ischemic tissues were taken for determining the activities of AST, CK, CK-MB, LDH, LDH1, SOD, GSH-Px, TNOS and ATPase, and content of MDA and NEFA. 4. The myocardial ischemic tissues were taken for determining Bcl-2 and Bax protein expressions by immunohistochemical method.
Results: 1. Compared with MIRI group, at 180min after reperfusion, HR, LVSP, +dp/dtmax and ET in PLFH group increased significantly (P<0.01 or P<0.05), while the Lvedp, -dp/dtmax, IT, IT/ET decreased significantly (P<0.01 or P<0.05). 2. Myocardial fibers were in disorder condition under optical microscope in MIRI group, in which cellular edema, break or necrosis, infiltration of inflammatory cells, or obvious leakage of red blood cells could be observed. The above injuries could be significantly alleviated in PLFL and PLFH group. The obvious damages of myocardial fibers, mitochondria and intercalated disks could be observed in MIRI group under electronic microscope, but these damages were attenuated significantly in PLFL and PLFH group. 3. Compared with MIRI group, persimmon leaf flavonoid could inhibited the increasing of myocardial enzyme activity and the content of MDA in the serum significantly (P<0.01), and inhibited the decreasing in the activities of SOD, GSH-Px and TNOS in the serum significantly (P<0.01 or P<0.05). Persimmon leaf flavonoid also could decrease the content of MDA and NEFA in the myocardial ischemic tissues significantly (P<0.01 or P<0.05), and increase the myocardial enzyme activity and the activities of SOD, GSH-Px and ATPase in the myocardial ischemic tissues(P<0.01 or P<0.05). 4. Compared with the MIRI group, the expression of Bc1-2 protein increased significantly in PLFL and PLFH group (P> 0.05), the expresion of NF-κBp65 protein,Bax protein and the ratio of Bax protein to Bc1-2 decreased significantly (P <0.05),
Conclusion: Persimmon leaf extracts have the protective effects on myocardial ischemical reperfusion injury in dogs. The mechanism may be related to anti-oxidation, protect the activity of ATPase, decrease the content of NEFA, increase the activity of TNOS, improve hemodynamics of heart and inhibit the cardiocyte apoptosis.
引文
[1]李莉,王钦茂.抗高血压中药的研究现状[J].中国临床药理学与治疗学,2002,7(1):94-96
[2]段小群,焦杨,黄仁彬,等.玉郎伞提取物对大鼠自发性高血压的影响[J].广西医科大学学报,2003,20(1):18-20
[3]黄仁彬,林兴,蒋伟哲,等.玉郎伞化学成分对自发性高血压大鼠血压的影响[J].中国医院药学杂志,2006,26(2):130-133
[4]黄仁彬,焦杨,蒋伟哲,等.玉郎伞提取物对心脏血流动力学和冠脉流量的影响[J].中国医院药学杂志,2003,23(6):321-322
[5]焦杨,段小群,孔晓龙,等.玉郎伞提取物对大鼠心肌缺血再灌注损伤的保护作用[J].中国医院药学杂志,2004,24(12):726-727
[6] Wang QD, Pernow J, Sjoquist PO, et al. Pharmacological possibilities for protection against myocardial reperfusion injury [J]. Cardiovasc Res, 2002, 55(1): 25-37.
[7] Hess ML, Manson NH. Molecular oxygen: Friend and foe. The role of the oxygen free radical system in the calcium paradox, the oxygen paradox and ischemia and reperfusion injury [J]. J Mol Cell Cardiol, 1984, 16(11): 969-985
[8] Kato R, Foex P.Myocardial protection by anesthetic agents against ischemia/reperfusion injury: an update for anesthesiologists [J]. Can J Anaesth, 2002, 49(8): 777-791
[9]吴其下,余应年,卢建.新编病理生理学[M].北京:中国协和医科大学出版社, 1999: 191-200.
[10] Mehlhom U, B loch W, Krahwinkel A, et al. Activation of myocandial constitutive nitric oxide synthase during coronary artery surgery[J]. Eur J Cardio Thorac Surg, 2000, 17(3): 305-311.
[11] Wang WJ, Sawicki G, Schulz R. Peroxynitrite-induced myocardial injury is mediated through matrixmetslloproteinase-2[J]. Cardiovasc Res, 2002, 53(1): 165-174.
[12] Liu PT, Xu BH, Cavalieri TA, et al. Hock, age-related difference in myocardial function and inflammation in a rat model of myocardial ischemia-reperfusion [J]. Cardiovasc Res, 2002,56(3): 443-453.
[13] Bolli R. Cradioprotective function of inducible nitric oxide synthase and role of nitric oxide in myocardial ischemia and preconditioning: an overview of a decade of research [J]. J Mol Cell Cardiol, 2001, 33(11): 1897-1918.
[14] Bolli R, Marban E. Molecular and cellular mechanisms of myocardial stunning. Physiol Rev, 1999, 79(2): 609-634.
[15] Van Eyk JE, Powers F, Law W, et al. Breakdown and release of myofilament proteins during ischemia and ischemia/reperfusion in rat hearts: identification of degradation products and effects on the pCa-force relation. Circ Res, 1998, 82(2): 261-271.
[16] Liu B, Clanachan AS, Schulz R, et al. Cardiac efficiency is improved after ischemia by altering both the source and fate of protons. Circ Res, 1996, 79(5):940-948.
[17] Cook SA, Sugden PH, Clerk A. Regulation of Bcl-2 family proteins during development and in response to oxidative stress in cardiac myocytes: association with changes in mitochondrial membrane potential [J]. Circ Res, 1999, 85(10): 940-949
[18] Kwak HB, Song W, Lawler JM. Exercise training attenuates age-induced elevation in Bax/Bcl-2 ratio, apoptosis, and remodeling in the rat heart [J]. FASEB J, 2006, 20(6): 791-793
[19] Niu J, Azfer A, Kolattukudy PE. Monocyte-specific Bcl-2 expression attenuates inflammation and heart failure in monocyte chemoattractant protein-1 (MCP-1) induced cardiomyopathy [J]. Cardiovasc Res, 2006, 71(1): 139-148
[20] Gupta S, Knowlton AA. HSP60, Bax, apoptosis and the heart [J]. J Cell Mol Med, 2005, 9(1): 51-58
[21]屈朝法,马礼坤,徐少东,等.急性心肌梗死延迟再灌注后心肌细胞凋亡与bcl-2和bax基因mRNA表达的研究[J].临床心血管病杂志,2006,22(12): 747-749
[22] Kobara M, Tatsumi T, Kambayashi D, et al. Effects of ACE inhibition on myocardial apoptosis in an ischemia-reperfusion rat heart model [J]. J Cardiovasc Pharmacol, 2003, 41(6): 880-889
[23] Kukhta VK, Marozkina NV, Sokolchik IG, et al. Molecular mechanisms of apoptosis [J]. Ukr Biokhim Zh, 2003, 75(6): 5-9
[24] Dlamini Z, Mbita Z, Zungu M.Genealogy, expression and molecular mechanisms in apoptosis [J]. Pharmacol Ther, 2004, 101(1): 1-15
[25] Goga LM, Vasiliu OM, Ionescu CR. Molecular mechanisms of apoptosis. Fas and TNF systems. ICE protease system. Bcl-2 family [J]. Rev Med Chir Soc Med Nat Iasi, 2001, 105(1): 23-29
[26] Machy TJ, Borkowski A, Amin, et al. Bc1-2/Bax ratio as a predictive marker for the rapeutic response to radiotherapy in patients with prostate cancer [J]. Urologe, 1998, 56(2): 1085
[27]徐祥,梁华平.核因子-κB的结构和功能研究进展[J].细胞与分子免疫学杂志,2002,18(1):254-260
[28]庞涛,陈婉蓉.线粒体与细胞凋亡的研究进展[J].卫生毒理学杂志, 2003,17(2):122-124.
[29] Schonfeld P, Schild L, Bohnensack R. Expression of the ADP/ATP carrier and expansion of the mitochondrial (ATP+ADP) pool contribute to postnatal maturation of the rat heart [J]. Eur J Biochem, 1996, 241(3): 895-900.
[30]李兵,柳君泽,陈丽芬.缺氧对大鼠心肌线粒体能量代谢和腺苷酸转位酶活性的影响[J].中国病理生理杂志,2006,22(3):460-463.
[31] Ning XH, Xu CS, Song YC, et al. Hypothermia preserves function and signaling for mitochondrial biogenesis during subsequent ischemia [J]. Am J Physiol, 1998, 274 (3 Pt 2): H786-93.
[32]殷仁富,陈金明.心肌能量学—代谢与治疗[M].上海:第二军医大学出版社, 2002.125-126.
[33] Tanaka M, Fuentes ME, Yamaguchi K, et al. Embryonic lethality, liverdegeneration, and impaired NF-kappa B activation in IKK-beta-deficient mice [J]. Immunity, 1999, 10(4): 421-9.
[34] Yin MJ, Yamamoto Y, Gaynor RB. The anti-inflammatory agents aspirin and salicylate inhibit the activity of I (kappa) B kinase-beta [J]. Nature, 1998, 396(6706): 77-80.
[35]张艳,陈栋,贡福盛,等. RNAi介导Caspase-3基因及其一致LPS诱导肾脏上皮细胞凋亡的研究[J].中国免疫学杂志,2008,24(1):16-19.
[36] Rupinder SK, Gurpreet AK, Manjeet S. Cell suicide and caspases[J].Vascul pharmacol, 2007, 46(6):383-393.
[37]陈永香,吴国远.缺氧缺血对新生大鼠脑组织半胱氨酸蛋白水解酶激活因子蛋白表达的影响[J].实用儿科临床杂志, 2008, 23(2):131-132.
[38] Lakhani SA, Masud A, Kuida K, et al. Caspases 3 and 7: key mediators of mitochondrial events of apoptosis [J]. Science, 2006, 311(5762): 847-51.
[39]姜明,曹士奇,陈锁成,等. Caspase-3抑制剂对兔体外循环心肌细胞凋亡的影响[J].江苏大学学报:医学版,2007,17(3),205-208.
[40]张素清,姜良铎,徐建兴.线粒体、活性氧与心肌缺血再灌注损伤[J].医学研究杂志,2006,35(9):84-86.
[41]李敬远,王俊科,曾因明.心肌缺血再灌注损伤的线粒体通透性转换机制[J].国际麻醉学与复苏杂志,2006,27(1):54-57.
[42]赵新,曾玉杰.心脏缺血再灌注心律失常与心肌超微结构改变关系的研究[J].中西医结合心脑血管病杂志,2005,3(7):608-610.
[43]赵明,张顺业,魏艳红.促红细胞生成素在大鼠心肌缺血再灌注损伤过程中的保护作用[J].中西医结合心脑血管病杂志,2008,6(2):184-186.
[1]唐红,黄鹤,张嬿，等.实验恒河猴10只心脏血流动力学及左室收缩功能的初步测定[J].中国比较医学杂志,2005,15(5):298-301.
[2]周燕琼,石刚刚,高分飞,等.碘化N-正丁基氟哌啶醇对大鼠心肌缺血再灌注损伤血流动力学的影响[J].中国药理学通报,2004,20(4):449-452.
[3]杨迪成,肖明第,卢成宝.心肌缺血-再灌注模型血流动力学的实验研究.医学研究生学报,19(6),2006. 524-525,529.
[4]周远鹏,江京莉.大豆黄酮对麻醉犬心脏血流动力学的影响[J].中国药理学与毒理学杂志,1990,4(3):229-230.
[5]李乐,孙晓东,高晓利,等.绞股蓝总黄酮对麻醉犬心脏血流动力学及冠脉血流量的作用[J].浙江工业大学学报,2006,34(5):521-524,528.
[6]梁催,符福民.柿叶对心血管系统的药理作用[J].药学通报,1985,20(4):245.
[7]韩克慧,韩道昌,张益民.柿树的药理与临床应用[J].中成药研究,1983,7(1):27-28.
[8]姚泰.生理学[M].北京:人民卫生出版社,2004:101.
[9]李恩,王世昌.基础临床与专题讲座.北京:人民卫生出版社. 1984:120.
[10] Sato H, Zhao Z Q, McGee D S, et al. Supplemental Larginine during cardiop legic arrest and reperfusion avoids regional postischemic injury[J]. Thorac Cardiovass Surg, 1995, 110(2): 302-312.
[11] Fye WB. Cardiovascular pharmacology: a historical perspective[M]. IN: Fishman WH, SonneblickEH. ed. Cardiovascular pharmacotherapy. New York: Mc Graw-Hill, 1997. 47-54.
[12]汪华君,戴淑芳,王丽,等.茶多酚对麻醉大鼠血流动力学的影响[J].大连医科大学学报,2006,28(2):104-108.
[1]龚明玉,袁亚飞,周晓慧,等.黄芩茎叶总黄酮预处理对大鼠缺血再灌注心肌细胞凋亡的影响[J].陕西医学杂志,2007,36(12): 1592-1594,1616.
[2]赵明,于影,邵慧杰,等.黄芪总黄酮对大鼠实验性心律失常的保护作用[J].中国心血管病研究杂志,2007,5(12):918-919.
[3]刘永平,宋成军,赵淑敏,等. SSTF预处理对缺血再灌注心肌超微结构及细胞凋亡的保护作用[J].中国中医基础医学杂志,2006,12(9):677-679.
[4]赵艳芳,秦永文,王学敏,等.曲美他嗪对大鼠缺血再灌注心肌线粒体的保护作用[J].医学研究生学报,2005,18(B05):11-13,16.
[5]赵淑敏,孔祥玉,周健,等.黄芪预处理对缺血再灌注大鼠心肌超微结构的保护作用[J].中国临床康复,2005,9(27):80-81.
[6]张素清,姜良铎,徐建兴.线粒体、活性氧与心肌缺血再灌注损伤[J].医学研究杂志,2006,35(9):84-86.
[7]李敬远,王俊科,曾因明.心肌缺血再灌注损伤的线粒体通透性转换机制[J].国际麻醉学与复苏杂志,2006,27(1):54-57.
[8]赵新,曾玉杰.心脏缺血再灌注心律失常与心肌超微结构改变关系的研究[J].中西医结合心脑血管病杂志,2005,3(7):608-610.
[9] Yeager M. Structure of cardiac gap junction intercellular channels [J]. J Struct Biol, 1998, 121(2): 231-45.
[1] Ma XL, Weyrich AS, Lefer DJ, et al. Diminished basal nitric oxide release after myocardial ischemia and reperfusion promotes neutrophil adherence to coronary endothelium. Circ Res, 1993, 72(2):403.
[2] Wolff AA, et al. Metabolic approaches to treatment of ischemic heart disease: the clinicans’perspective. Heat FA L Rev, 2002, 7(2): 187.
[3]刘德麟.分子网络紊乱与调节[M].北京:清华大学出版社,1999:63.
[4]王成天,陈峰,王嵌林,等.当归注射液,三七总皂苷和外源性环磷酸腺苷对大鼠心肌缺血再灌注损伤的保护作用[J].中国临床康复,2004,8(15):2859-2871.
[5] Zhao AQ, Jakob VJ. Post conditioning: reduction of reperfusion-induced injury[J]. Cardiovasc Res, 2006, 70: 200-202.
[6] [Zubgarelli, Basilia, Hake, Paul W, et al. Inducible Nitric Oxide Synthase Is Not Required in the Development of Endotoxin Tolerance in Mice[J]. Shock. 17(6):478-484, June 2002.
[7] Michael C, Robert L, Anderson F, et al. Comparison of myocardial perfusion imaging and cardiac troponin I in patients admitted to the emergency department with chest pain[J].Circulation. 1999, (16):2073-2078.
[8] Vongvanich,Piyanuj MD,Merz C. Supervised Exercise and electrocardiographic monitoring during cardiac rehabilitation: IMPACT ON PATIENT CARE[J]. Journal of Cardiopulmonary Rehabilitation. 1996,16(4): 233-238。
[9]张而立,李松,陈畅,等.一氧化氮与细胞凋亡的关系及研究进展[J].中国生化药物杂志,2007,28(6):427-429.
[10]史树贵.一氧化氮与细胞凋亡[J].国外医学:生理病理科学与临床分册,1997,17(3): 267-270.
[11] Izhar U, Schwalb H, Borman JB, et al. Cardioprotective effect of L & shy: arginine in myocardial ischemia and reperfusion in an isolated working rat heart model[J]. J Cardiovasc Surg, 1998, 39: 321-329.
[12] Xuan YT, Tang XL, Qiu Y, et al. Biphasic response of cardiac NO synthase isoforms to ischemic preconditioning in consicious rabbits[J]. Am J Physiol Heart Circ Physiol, 2000. 279: 2360-2371.
[13]金惠铭,王建枝.病理生理学.第六版.北京:人民卫生出版社,2003: 207-208.
[14] Netticadan T, Temsah R, Osada M, et al. Status of Ca2+ / calmodulin protein kinase phosphorylation of cardiac SR proteins in ischemia - reperfusion. Am J Physiol, 1999, 277(3 Pt 1): C384.
[1] Misso J, Hayakawa Y, Ohno M, et al. Expression of bcl-2 protein, an inhibitor of apoptosis and Bax, an accelerator of apoptosis, in ventricular myocytes of human hearts with myocardial infarction [J]. Circulation, 1996,94(7):1506-1512.
[2] Rezvani M, Barrans J D, Dai K S, et al. Apoptosis-related genes expressed in cardiovascular development and disease: all EST approach[J]. Cardiovasc Res,2002,45(3):621-629.
[3] Yang E, Korsmeyer SJ. Molecular thanatopsis: a discourse on the bcl-2 family and cell death[J]. Blood,1996,88(2):386-401.
[4] Oltvai Zn, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death[J]. Cell, 1993,74(4):609-619
[5] Borutaite V, Brown GC. Mitochondria in apoptosis of ischemic heart[J]. FEBS Lett, 2003, 541(1-3): 1-5.
[6]吴青,陶宏凯,陶大昌,等.缺血再灌注诱导心肌细胞凋亡及凋亡相关基因表达的研究[J].中国心血管病研究杂志,2004,2(11):905-908
[7] Valen G. Signal transduction through nuclear factor kappa B in ischemia-reperfusion and heart failure. Basic Res Cardiol, 2004, 99:1-7.
[8]马中富,马虹,叶任高,等.实验性心肌梗塞心肌细胞凋亡的研究.中国急救医学.1999,19(10):577-580.
[9] Soloviev A, Stefanov A, Parshikov A, et al. Arrhythmogenic peroxynitrite-induced alterations in mammalian heart contractility and its prevention with quercetin-filled liposomes [J]. Cardiovasc Toxicol, 2002, 2(2): 129-39.
[10]杨彦玲,李建龙,等.心肌缺血再灌注损伤研究进展[J].心血管病学进展,2003,24(2):116-121.
[11] Borutaite V, Brown GC. Mitochondria in apoptosis of ischemic heart[J]. FEBS Lett, 2003, 541(1-3): 1-5.
[12]吴青,陶宏凯,陶大昌,等.缺血再灌注诱导心肌细胞凋亡及凋亡相关基因表达的研究[J].中国心血管病研究杂志,2004,2(11):905-908.
[13] Onai Y, Suzuki J, Maejima Y, et al. Inhibition of NF-kappa B improves left ventricular remodeling and cardiac dysfunction after myocardial infarction. Am J Physiol Heart Circ Physiol, 2007, 292: H530-538.
[14] Schmidt KN, Traenckner EBM, Meier B, et al. Induction of oxidatives tress by odadaic acid is required for activation of transcriotion factor NF-κB. J Biol Chem. 1995, 27: 36-42.
[15]查锡良,药立波,冯作化,等.医学分子生物学[M].北京:人民卫生出版社. 2005:426-427.
[16] Pye J, Ardeshirpour F, McCain A, et al. Proteasome inhibition ablates activation of NF-kappa B in myocardial reperfusion and reduces reperfusion injury. Am J Physiol Heart Circ Physiol, 2003, 284: 919-926.
[1] Sekikawa A, Horiuchi BY, Edmundowicz D, et al. A "natural experiment" in cardiovascular epidemiology in the early 21st century [J]. Heart, 2003, 89(3): 255-7.
[2]孙涛.自由基与心肌缺血/再灌注损伤[J].实用医院临床杂志, 2006, 3(4): 94-96.
[3]刘镇,连俊兰,雷健.心肌缺血再灌注炎症损伤机制的研究进展[J].中国心血管病研究杂志,2004,2(11):909-912.
[4]孙炎华.神经肽Y对心肌缺血再灌注损伤内皮功能影响的研究现状[J].医学综述,2007,13(10):727-729.
[5] Petrosillo G, Ruggiero FM, Di Venosa N, et al. Decreased complex III activity in mitochondria isolated from rat heart subjected to ischemia and reperfusion: role of reactive oxygen species and cardiolipin [J]. FASEB J, 2003, 17(6): 714-6.
[6]朱静峰,黄冬.氧自由基、钙超载与心肌缺血再灌注损伤[J].云南医药,2007,28(1):67-70.
[7]王雅锋.钠/钙和钠/氢交换蛋白与心肌缺血再灌注损伤[J].医学综述,2007,13(5):368-370.
[8]朱妙章,袁文俊,吴博威,等.血管生理与临床[M].第1版版.北京:高等教育出版社,2004:300.
[9]徐冬梅,刘正湘.钙与心肌缺血再灌注诱发的心肌细胞凋亡[J].中国组织化学与细胞化学杂志,2000, 9(1):113-117.
[10]谷天祥,张显清,等.心肌缺血再灌注损伤亚细胞Ca2+反常与ATP酶泵功能抑制[J].中华心血管病杂志,2001,29(7):420-423.
[11]李春杰,余柏林.心肌缺血再灌注损伤机制研究进展[J].人民军医,2004,47(1):47-49.
[12]赵慧娟,龙明智.心肌缺血再灌注损伤机制的研究近况[J].中西医结合心脑血管病杂志,2005,3(3):240-242.
[13]黄兵.细胞粘附分子与心肌缺血再灌注损伤[J].国外医学:生理病理科学与临床分册,2001,21(3):195-197.
[14]朱彪.粘附分子和心肌缺血再灌注损伤的新进展[J].国外医学:麻醉学与复苏分册,2003,24(3):167-170.
[15]张而立,李松,陈畅,等.一氧化氮与细胞凋亡的关系及研究进展[J].中国生化药物杂志,2007,28(6):427-429.
[16]史树贵.一氧化氮与细胞凋亡[J].国外医学:生理病理科学与临床分册,1997,17(3):267-270.
[17] Ursell PC, Mayes M. Anatomic distribution of nitric oxide synthase in the heart[J]. Int J Cardiol, 1995, 50(3): 217-23.
[18] Balligand JL, Cannon PJ. Nitric oxide synthases and cardiac muscle. Autocrine and paracrine influences [J]. Arterioscler Thromb Vasc Biol, 1997, 17(10): 1846-58.
[19] Mehlhorn U, Bloch W, Krahwinkel A, et al. Activation of myocardial constitutive nitric oxide synthase during coronary artery surgery [J]. Eur J Cardiothorac Surg, 2000, 17(3): 305-11.
[20] Wang W, Sawicki G, Schulz R. Peroxynitrite-induced myocardial injury ismediated through matrix metalloproteinase-2 [J]. Cardiovasc Res, 2002, 53(1): 165-74.
[21] Heusch G, Post H, Michel MC, et al. Endogenous nitric oxide and myocardial adaptation to ischemia [J]. Circ Res, 2000, 87(2): 146-52.
[22] Bolli R. Cardioprotective function of inducible nitric oxide synthase and role of nitric oxide in myocardial ischemia and preconditioning: an overview of a decade of research [J]. J Mol Cell Cardiol, 2001, 33(11): 1897-918.
[23] Gewaltig MT, Kojda G. Vasoprotection by nitric oxide: mechanisms and therapeutic potential [J]. Cardiovasc Res, 2002, 55(2): 250-60.
[24] Pabla R, Curtis MJ. Effects of NO modulation on cardiac arrhythmias in the rat isolated heart [J]. Circ Res, 1995, 77(5): 984-92.
[25] Kawahara K, Takase M, Yamauchi Y. Increased vulnerability to ischemia/reperfusion-induced ventricular tachyarrhythmias by pre-ischemic inhibition of nitric oxide synthase in isolated rat hearts [J]. Cardiovasc Pathol, 2003, 12(1): 49-56.
[26] Zingarelli B, Hake PW, Yang Z, et al. Absence of inducible nitric oxide synthase modulates early reperfusion-induced NF-kappaB and AP-1 activation and enhances myocardial damage [J]. FASEB J, 2002, 16(3): 327-42.
[27] Martin C, Schulz R, Post H, et al. Microdialysis-based analysis of interstitial NO in situ: NO synthase-independent NO formation during myocardial ischemia [J]. Cardiovasc Res, 2007, 74(1): 46-55.
[28]王乐,曾秋棠,谢江.白藜芦醇预处理对体外大鼠心肌缺血再灌注损伤的保护作用[J].临床心血管病杂志,2006,22(1):47-49.
[29] Gao F, Gao E, Yue TL, et al. Nitric oxide mediates the antiapoptotic effectof insulin in myocardial ischemia-reperfusion: the roles of PI3-kinase, Akt, and endothelial nitric oxide synthase phosphorylation [J]. Circulation, 2002, 105(12): 1497-502.
[30] Jones SP, Greer JJ, Kakkar AK, et al. Endothelial nitric oxide synthase overexpression attenuates myocardial reperfusion injury [J]. Am J Physiol Heart Circ Physiol, 2004, 286(1): H276-82.
[31] Gok S, Vatansever S, Vural K, et al. The role of ATP sensitive K+ channels and of nitric oxide synthase on myocardial ischemia/reperfusion- induced apoptosis [J]. Acta Histochem, 2006, 108(2): 95-104.
[32]英明中,李小鹰,陈孝,等.一氧化氮对心肌缺血/再灌注损伤细胞凋亡和心功能的影响[J].中国应用生理学杂志,2004,20(1):34-36.
[33] Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease [J]. Physiol Rev, 2007, 87(1): 315-424.
[34] Pryor WA, Squadrito GL. The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide [J]. Am J Physiol, 1995, 268(5 Pt 1): L699-722.
[35]周玫,陈瑗.体内一氧化氮和过氧亚硝酸的生成及其生物学效应[J].中国动脉硬化杂志,1998,6(2):178-181.
[36] Oyama J, Shimokawa H, Momii H, et al. Role of nitric oxide and peroxynitrite in the cytokine-induced sustained myocardial dysfunction in dogs in vivo [J]. J Clin Invest, 1998, 101(10): 2207-14.
[37] Ishida H, Genka C, Hirota Y, et al. Distinct roles of peroxynitrite and hydroxyl radical in triggering stunned myocardium-like impairment of cardiac myocytes in vitro [J]. Mol Cell Biochem, 1999, 198(1-2): 31-8.
[38] Weyrich AS, Ma XL, Buerke M, et al. Physiological concentrations of nitric oxide do not elicit an acute negative inotropic effect in unstimulatedcardiac muscle [J]. Circ Res, 1994, 75(4): 692-700.
[39]吴青,陶宏凯,游敏,等.心肌缺血再灌注损伤时钙离子、氧自由基及一氧化氮变化的意义[J].中华实用中西医杂志,2004,17(11):1629-1631.
[40] Cuong DV, Kim N, Youm JB, et al. Nitric oxide-cGMP-protein kinase G signaling pathway induces anoxic preconditioning through activation of ATP-sensitive K+ channels in rat hearts [J]. Am J Physiol Heart Circ Physiol, 2006, 290(5): H1808-17.
[41] Hu A, Jiao X, Gao E, et al. Chronic beta-adrenergic receptor stimulation induces cardiac apoptosis and aggravates myocardial ischemia/reperfusion injury by provoking inducible nitric-oxide synthase-mediated nitrative stress [J]. J Pharmacol Exp Ther, 2006, 318(2): 469-75.
[42] Bengoechea-Alonso MT, Pelacho B, Oses-Prieto JA, et al. Regulation of NF-kappaB activation by protein phosphatase 2B and NO, via protein kinase A activity, in human monocytes [J]. Nitric Oxide, 2003, 8(1): 65-74.
[43] Wang D, Yang XP, Liu YH, et al. Reduction of myocardial infarct size by inhibition of inducible nitric oxide synthase [J]. Am J Hypertens, 1999, 12(2 Pt 1): 174-82.
[44] Saito T, Hu F, Tayara L, et al. Inhibition of NOS II prevents cardiac dysfunction in myocardial infarction and congestive heart failure [J]. Am J Physiol Heart Circ Physiol, 2002, 283(1): H339-45.
[45] Wildhirt SM, Weismueller S, Schulze C, et al. Inducible nitric oxide synthase activation after ischemia/reperfusion contributes to myocardial dysfunction and extent of infarct size in rabbits: evidence for a late phase of nitric oxide-mediated reperfusion injury [J]. Cardiovasc Res, 1999, 43(3): 698-711.
[46] Feng Q, Lu X, Jones DL, et al. Increased inducible nitric oxide synthase expression contributes to myocardial dysfunction and higher mortality after myocardial infarction in mice [J]. Circulation, 2001, 104(6): 700-4.
[47] Dawson D, Lygate CA, Zhang MH, et al. nNOS gene deletion exacerbates pathological left ventricular remodeling and functional deterioration after myocardial infarction [J]. Circulation, 2005, 112(24): 3729-37.
[48] Massion PB, Pelat M, Belge C, et al. Regulation of the mammalian heart function by nitric oxide [J]. Comp Biochem Physiol A Mol Integr Physiol, 2005, 142(2): 144-50.
[49]李萍,富青,熊凡.热休克蛋白70在大鼠心肌缺血再灌注过程中的表达及其意义[J].微循环学杂志,2004,14(3):39-41,F009.
[50] Jugdutt BI. Nitric oxide and cardioprotection during ischemia-reperfusion [J]. Heart Fail Rev, 2002, 7(4): 391-405.
[51] Schulz R, Kelm M,Heusch G. Nitric oxide in myocardial ischemia/ reperfusion injury [J]. Cardiovasc Res, 2004, 61(3): 402-13.
[52] Soloviev A, Stefanov A, Parshikov A, et al. Arrhythmogenic peroxynitrite- induced alterations in mammalian heart contractility and its prevention with quercetin-filled liposomes [J]. Cardiovasc Toxicol, 2002, 2(2): 129-39.
[53]杨彦玲,李建龙,等.心肌缺血再灌注损伤研究进展[J].心血管病学进展,2003,24(2):116-121.
[54] Bishopric NH, Andreka P, Slepak T, et al. Molecular mechanisms of apoptosis in the cardiac myocyte [J]. Curr Opin Pharmacol, 2001, 1(2): 141-50.
[55] Gustafsson AB, Gottlieb RA. Mechanisms of apoptosis in the heart [J]. J Clin Immunol, 2003, 23(6): 447-59.
[56]刘胜中.细胞凋亡与心肌缺血/再灌注损伤[J].心血管病学进展,2007,28(4):613-617.
[57] Borutaite V, Brown GC. Mitochondria in apoptosis of ischemic heart [J]. FEBS Lett, 2003, 541(1-3): 1-5.
[58]吴青,陶宏凯,陶大昌,等.缺血再灌注诱导心肌细胞凋亡及凋亡相关基因表达的研究[J].中国心血管病研究杂志,2004,2(11):905-908.
[59]谭兴琴.凋亡因子bcl-2/bax与心肌缺血再灌注损伤[J].重庆医学,2007,36(18):1885-1887.
[60] Doerner A, Pauschinger M, Badorff A, et al. Tissue-specific transcription pattern of the adenine nucleotide translocase isoforms in humans [J]. FEBS Lett, 1997, 414(2): 258-62.
[61] Dorner A, Schulze K, Rauch U, et al. Adenine nucleotide translocator in dilated cardiomyopathy: pathophysiological alterations in expression and function [J]. Mol Cell Biochem, 1997, 174(1-2): 261-9.
[62] Turcotte ML, Parliament M, Franko A, et al. Variation in mitochondrial function in hypoxia-sensitive and hypoxia-tolerant human glioma cells [J]. Br J Cancer, 2002, 86(4): 619-24.
[63] Dorner A, Olesch M, Giessen S, et al. Transcription of the adenine nucleotide translocase isoforms in various types of tissues in the rat [J]. Biochim Biophys Acta, 1999, 1417(1):16-24.
[64] Pereira C, Camougrand N, Manon S, et al. ADP/ATP carrier is required for mitochondrial outer membrane permeabilization and cytochrome c release in yeast apoptosis [J]. Mol Microbiol, 2007, 66(3): 571-82.
[65] Schonfeld P, Schild L,Bohnensack R. Expression of the ADP/ATP carrier and expansion of the mitochondrial (ATP + ADP) pool contribute to postnatal maturation of the rat heart [J]. Eur J Biochem, 1996, 241(3): 895-900.
[66]李兵,柳君泽,陈丽芬.缺氧对大鼠心肌线粒体能量代谢和腺苷酸转位酶活性的影响[J].中国病理生理杂志,2006,22(3):460-463.
[67] Ning XH, Xu CS, Song YC, et al. Hypothermia preserves function and signaling for mitochondrial biogenesis during subsequent ischemia [J]. Am J Physiol, 1998, 274(3 Pt 2): H786-93.
[68] Bogazzi F, Raggi F, Ultimieri F, et al. Cardiac expression of adenine nucleotide translocase-1 in transgenic mice overexpressing bovine GH [J]. J Endocrinol, 2007, 194(3): 521-7.
[69] Esposito LA, Melov S, Panov A, et al. Mitochondrial disease in mouse results in increased oxidative stress [J]. Proc Natl Acad Sci U S A, 1999, 96(9): 4820-5.
[70] Tanaka M, Fuentes ME, Yamaguchi K, et al. Embryonic lethality, liver degeneration, and impaired NF-kappa B activation in IKK-beta-deficient mice[J]. Immunity, 1999, 10(4): 421-9.
[71] Yin MJ, Yamamoto Y,Gaynor RB. The anti-inflammatory agents aspirin and salicylate inhibit the activity of I (kappa)B kinase-beta [J]. Nature, 1998, 396(6706): 77-80.
[72]杭涛,江时森,等.腺嘌呤核苷酸转运体在压力负荷大鼠心肌组织中的表达[J].医学研究生学报,2003,16(2):97-100, 104.
[73] Bauer MK, Schubert A, Rocks O, et al. Adenine nucleotide translocase-1, a component of the permeability transition pore, can dominantly induce apoptosis [J]. J Cell Biol, 1999, 147(7): 1493-502.
[74] Vyssokikh MY, Katz A, Rueck A, et al. Adenine nucleotide translocator isoforms 1 and 2 are differently distributed in the mitochondrial inner membrane and have distinct affinities to cyclophilin D [J]. Biochem J, 2001, 358(Pt 2): 349-58.
[75] Marzo I, Brenner C, Zamzami N, et al. Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis [J]. Science, 1998, 281(5385): 2027-31.
[76] Belzacq AS, Vieira HL, Verrier F, et al. Bcl-2 and Bax modulate adenine nucleotide translocase activity [J]. Cancer Res, 2003, 63(2): 541-6.
[77] Mastrangelo AJ, Betenbaugh MJ. Overcoming apoptosis: new methods for improving protein-expression systems [J]. Trends Biotechnol, 1998, 16(2): 88-95.
[78]胡章乐,马礼坤. Caspase-3与心肌缺血/再灌注损伤[J].国际病理科学与临床杂志,2007,27(3):208-210.
[79] Lakhani SA, Masud A, Kuida K, et al. Caspases 3 and 7: key mediators of mitochondrial events of apoptosis [J]. Science, 2006, 311(5762): 847-51.
[80]姜明,曹士奇,陈锁成,等. Caspase-3抑制剂对兔体外循环心肌细胞凋亡的影响[J].江苏大学学报:医学版,2007,17(3):205-208.
[81]韩笑,刘建勋.心肌缺血再灌注损伤的细胞信号转导机制[J].中国药理学通报,2004,20(1):4-7.
1.黄成勇,玉郎伞的显微和紫外吸收光谱鉴定.中药材,2001,24(10):720-721
2.戴斌,丘翠嫦,戴向东,等.玉郎伞与水罗伞的生药学比较研究.中草药,38(12):1889-1892
3.林兴,蒋伟哲,焦杨,等.玉郎伞多糖化学成分的研究,中成药,2009,31(6):903-905
4.戴斌,丘翠嫦,戴向东,等.玉郎伞的化学成分分析.中国民族民间医药,2009,18(9):9
5.简洁,林兴,黄仁彬.玉郎伞总黄酮提取工艺研究.时珍国医国药,2009,20(8):1998-1999
6.段小群,焦杨,黄仁彬,等.玉郎伞提取物对大鼠自发性高血压的影响,广西医科大学学报,2003,20(1):18-20
7.黄仁彬,林兴,蒋伟哲,等.玉郎伞化学成分对自发性高血压大鼠血压的影响,中国医院药学杂志,2006,26(2):130-133
8.黄仁彬,焦杨,蒋伟哲,等.玉郎伞提取物对心脏血流动力学和冠脉流量的影响.中国医院药学杂志,2003,23(6):321-322
9.焦杨,段小群,孔晓,等.玉郎伞提取物对大鼠心肌缺血再灌注损伤的保护作用.中国医院药学杂志,2004,24(12):726-727
10.黄仁彬,张绪东,蒋伟哲,等.玉郎伞黄酮对心肌缺血再灌注损伤的保护作用,中国医院药学杂志,2008,28(11):870-873
11.简洁,刘曦,黄仁彬,等.玉郎伞两种黄酮单体对心肌细胞缺氧/复氧损伤的保护作用.中国药理学通报,2009,25(7):942-945
12.黄仁彬,段小群,焦杨,等.玉郎伞提取物对小鼠急性化学性肝损伤的保护作用及其机制的研究.广西医科大学学报,2003,20(6):874-877
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15.段小群,焦杨,张士军,等.玉郎伞多糖对过氧化氢诱导大鼠原代肝细胞损伤的保护作用.时珍国医国药,2007,18(7):1592-1593
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18.黄媛恒,陈健,黄仁彬,等.玉郎伞提取物抗炎作用及机制研究.中国新药杂志,2008,17(20):1764-1767
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21.陈健,黄媛恒,王乃平,等.玉郎伞多糖和皂苷对氧自由基清除作用研究.中药药理与临床,2007,23(5):100-102
22.简洁,李勇文,蒋伟哲,等.玉郎伞黄酮单体对自由基清除作用的实验研究.中国老年学杂志,2009,29(18):2353-2354
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24.欧灿纯,余术宜,黄建春,等.玉郎伞提取物的抗肝癌作用研究.中国药房,2009,20(27):2087-2089
25.桂茂林,冯自成,廉广,等.玉郎伞水提物对小鼠耐缺氧抗疲劳及耐高温能力的影响.时珍国医国药,2009,20(6):1394-1395
26.简洁,林兴,张士军,等.玉郎伞两种黄酮单体的抗氧化、耐缺氧和抗凝血作用研究.中药药理与临床,2009, 25(3):22-23
27.陈健,林兴,焦杨,等.玉郎伞多糖对大鼠局灶性脑缺血再灌注损伤的保护作用及机制初探.中国新药杂志,2008,17(13):1118-1120
28.梁霜,王乃平,黄仁彬,等.玉郎伞多糖抗抑郁作用研究.时珍国医国药,2010,21(1):241-242