尾加压素Ⅱ抑制大鼠心肌细胞L型钙电流

尾加压素Ⅱ(urotensinⅡ,UⅡ)是目前发现的哺乳动物体内强的缩血管物质,其缩血管效应比内皮素-1强10余倍[1].它具有收缩血管、促心肌细胞肥大和血管细胞增殖、抑制心功能等生物学效应,在高血压、动脉粥样硬化、心血管重塑、心力衰竭等多种心血管疾病的发生发展中可能具有重要意义.

刺五加皂甙B对心室肌细胞膜ATP敏感性钾通道的作用

刺五加皂甙B(acanthopanax senticosides B,Sb)是从刺五加的主要活性成分刺五加叶皂甙(ASS)中提取的一种单体,其分子式为C58H92O25·3H2O.ATP敏感性钾通道(KATP)开放剂能产生与缺血预处理(IP)类似的心肌保护作用,而ASS也有类似的心肌保护作用,因此本实验观察Sb对心肌细胞膜KATP的作用.

α1肾上腺素受体对豚鼠心肌细胞延迟整流钾电流的调控

人心肌上主要存在α1肾上腺素受体,生理状况下,α1受体激动不引起心肌的异常电活动,但在心肌缺血时,由于局部儿茶酚胺聚集,受体密度增加,使其作用增强,并因为心肌对α1受体作用反应的不一致性,可能引起致命的心律失常.

二十二碳六烯酸对心室肌细胞离子通道的影响

近年来,n-3多不饱和脂肪酸(n-3PUFAs)对心血管的有益作用已受到广泛重视.大量研究表明n-3PUFAs具有抗心律失常作用,能降低冠心病的猝死率及心肌梗死后恶性心律失常的发生率[1].基于这些研究结果,在心血管疾病的一级和二级预防中,美国和欧洲等心脏病学会推荐每日摄入小剂量n-3PUFAs[2].目前,n-3PUFAs抗心律失常的机制仍不完全清楚.n-3PUFAs主要包括二十二碳六烯酸(DHA)和二十碳五烯酸(EPA).本文通过膜片钳技术探讨DHA对大鼠心室肌细胞静息电位(RP)、动作电位时限(APD)、延迟整流性钾通道电流(IK)及内向整流性钾通道电流( IKl)的影响,阐述DHA抗心律失常的可能机制.1.材料和溶液组成:Axopatch 700B膜片钳放大器、Digi-Data 1322型数/模(或模/数)转换器、pClamp 9.0脉冲发放和数据采集软件(美国Axon Instruments公司).DHA(美国Sigma公司)以无水乙醇配制成50 mmol/L的母液,分装避光保存于-80℃备用.使用时无水乙醇的终浓度＜0.4％,以避免无水乙醇对离子通道的影响.牛血清白蛋白(BSA,美国Sigma公司)配制成2 mg/ml,4℃保存.

黄芪对急性心肌梗死兔心室肌细胞L-钙通道电流的影响

急性心肌梗死(AMI)后可发生各种心律失常,特别是折返性室性心律失常,是AMI严重的并发症之一.文献报道,AMI后梗死区内部及梗死周边区尚存活的心肌细胞L-钙通道电流(ICa-L)活性明显下降,形成心肌梗死后电重构,是AMI后发生心律失常的离子机制.本实验应用膜片钳全细胞记录方法,研究黄芪对AMI后1周ICa-L活性的变化,旨在为临床上应用黄芪治疗AMI提供理论依据.

山西医科大学循环生理研究室在国家级杂志和国外杂志已发表的科研学术论文

1979年前20年发表的文章：　1.超声波对大脑皮层机能活动的影响.生理学报，1962，25(2)：102～107．　2.氯丙嗪对兔皮层诱发电位影响的分析.生理学报，1965，28(1)：1～5．　3.抑制针麻时腹肌紧张的实验研究.新医药杂志，1975，（3）．　4.抑制内脏牵拉性腹肌紧张的实验研究.中华医学杂志，1977，57(11)：664～667 ．　5.抑制牵拉性腹肌紧张的实验研究.针刺麻醉，1977， （2）．1979年后发表的文章：　6.吴博威，李亮，赵荣瑞. 收缩能药物对心缩间期与心舒间期指标的影响. 中华心血管病杂志， 1979，7(4)：283～286.　7.赵荣瑞，吴博威，赵志青. 利用吸引电极记录家兔在体心脏单相动作电 位的实验分析. 生理学报，1983，35：116～120.　8.吴博威，赵志青，赵荣瑞. 在体兔心急性心肌缺血时的复极后不应性.生 理学报，1983，35：319～325.　9.马新亮，李亮，赵荣瑞，孙本韬. 兔心肌局部缺血和缺氧时的电活动与 超微结构的变化.生理学报，1983，35：460～465.10.赵志青，吴博威，赵荣瑞. 葡萄糖-胰岛素-钾溶液对缺血心肌电生理学变化的 影响. 中华心血管病杂志，1984，12：134～137.11.赵志青，王若翔，吴博威，赵荣瑞. 肉毒硷对兔在体缺血心室肌细胞动作电位的 影响.药学学报，1985，20：491～494.12.马新亮，赵敏奇，赵荣瑞. 狗急性心肌缺血早期冠脉侧枝血流量与血液流变学变 化的关系.生理学报，1985，37(6)：553～559.13.马新亮，赵荣瑞. 局部缺血、缺氧、高血钾和乳酸性酸中毒对在体兔心电活动的 影响.中华心血管病杂志，1985，13(7)：298.14.赵荣瑞，马新亮. α和β受体阻断剂对早期缺血心肌多发早搏阈的影响.生理学 报，1986，38(1)：66～74.15.赵志青，王若翔，赵荣瑞. 在体兔心左室肌缺血中心区与边缘区跨膜电位的比较 .生理学报，1986，38(2)：174～180.16.马新亮，赵荣瑞，孙本韬. 等容血液稀释对心肌缺血早期冠脉侧枝血流量与心肌 损伤的改善作用.中国病理生理杂志，1986，2(4)：212～217.17.马新亮，赵荣瑞，臧益民，王复周. 氟碳乳剂稀释血液对心肌缺血时左心室舒张 功能的影响.药学学报，1987，22(10)：721～724.18.马新亮，赵荣瑞，臧益民，王复周. 氟碳乳剂与右旋糖酐对犬缺血心肌侧枝循环 供氧的影响.生理学报，1987，39(3)：242～247.19.马新亮，赵荣瑞，臧益民，王复周. 右旋糖酐与氟碳乳剂稀释血液对心肌缺血时 全血黏度与侧枝循环影响的比较. 药学学报，1987，22(9)：641～644.20.吴博威，赵志青，王若翔，马新亮，赵荣瑞. 氟碳代血液灌流冠脉对兔心电生理 特性的影响.中国药理学报，1987，8(6)：5.21.Zhao RR, Ma XL, Zang YM, Wang FZ. 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Comparative study of transmembrane potential recorded from central ischemic zone and ischemic border zone of rabbit ′s heart.J Mol Cell Cardiol， 1987, 19(suppl I):S32.26. Ma XL, Zhao RR. Zang YM, Zhu MZ, Wang FZ. 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Cocaine depresses the canine my ocardium.Circulatory Shock， 1989， 28：309319.53.赵志青，朱妙章，臧益民，王复周.脾切除对狭窄冠脉血流量的影响.中国循环杂 志，1990，5(3)：224～228.54.赵志青，刘冰，赵荣瑞，朱妙章，臧益民.阿司匹林精氨酸对犬缺血心肌舒张功 能的影响.中国药学杂志，1990，25(3)：143～146.55.任文智，马新亮，赵荣瑞.血浆游离脂肪酸升高对急性缺血兔心脏收缩和舒张功 能的影响.中国应用生理学杂志，1990，6(3)：283～285.56.Cao JM,Zhao RR,Wu BW. Analysis of the protective effects of magnesium on cardiac electrophysiologic changes during myocardial hypoxia. Chin J Physiol Sci，1990， 6(2):108～112.57.Zhao RR, Fennell WH,Abel FL. Effects of dopamine D1 and D2 recepto r ag onists on coronary and peripheral hemodynamics. Europ J Pharmacol， 1990，190:19 3～202.58.Ma JH,Zhao RR. Responses of delayed after depolarization and triggeere d activity to programmed stimulation in guinea pig papillary muscles. Chin J Phy siol Sci， 1991，7(4):356～362.59.周颖盈，吴博威，赵荣瑞，赵志青，臧益民，朱妙章. 江浙蝮抗栓酶对兔缺血心 肌电生理学变化的影响.中国应用生理学杂志，1991，7(2)：129～133.60.赵志青，秦富忠，周颖盈，张炜芳，赵荣瑞，王峰峰. 阻断犬冠脉后冠状静脉血 液中影响血小板功能变化的因素分析.中国应用生理学杂志，1992，8(2)：135～139.61.马季骅，赵荣瑞. 基本刺激周长对豚鼠乳头肌两种触发性二联律的影响. 中国应 用生理学杂志，1992，8(2)：175～176.62.Zhao RR, Wang PH, Zhang WF， Fennell WH.Analysis of the effects of dop amine-1 and dopamine-2 receptor agonists on coronary flow. Meth Find Exp Clin Pharmacol， 1992，14(1):5～11.63.Qin FZ, Zhao RR. Effects of reduced red cell deformability on coronary hemodynamics and cardiac function.Clin Hemorheol， 1994， 14(6):779～787.64.Wang WZ, Zhao RR, Qin FZ. Comparison of the effects of dopamine l－and dopamine2－receptor agonists on the cAMP generating system in canine coronary a nd renal arteries. Mety Find Exp Clin Pharmacol， 1994， 16(10):691～696. 65.Qin FZ,Gao Z,Zhao RR. Comparison of dopexamine hydrochloride,fenoldopa m,and procaterol on myocardial nutritional flow in rats. Acta Pharmalogica Sinic a， 1994， 15(5):416～418.66.秦富忠，赵荣瑞，朱琳，王文泽，吴博威. 多培沙明、非诺多泮和丙卡妥罗对心 肌缺血时电生理变化影响的比较. 药学学报，1995，30(3)：161～167.67.秦富忠，赵荣瑞，赵志青，马新亮.急性心肌缺血时红细胞变形性的变化及其机 理.中国病理生理杂志，1996，11(1)：21～25.68.吴博威，赵荣瑞. Mg2+对豚鼠心室肌细胞ATP敏感钾电流的抑制作用.中国应用生理学杂志，1993，9(2)：107～111.69.吴博威，盛秉通，王文泽，赵荣瑞.妥卡尼对豚鼠心室肌细胞钙电流和钾电流的 抑制作用.药学学报，1995，30(6)：412～416.70.马季骅，赵荣瑞.心肌缺血时心室肌细胞的动作电位交替与镁的抗电交替作用.中国病理生理杂志，1994，10(4)：409～412.71.Zhu L,Zhao RR,Wang WZ.Comparative studies on the characteristics of do pamine receptors in different vascular systems.Chin J Physiol Sci， 1995，11(1): 81～89.72.Zhu L,Zhao RR,Qing FZ. Nitric oxide as a mediator of endothelial dopam ine D1 receptors in rabbit pukmonary artery. Chin J Physiol Sci， 1996，12(2): 157～162.73.Zhao RR,Zhao ZQ, Zhang WF, Ma XL. Changes in erythrocyte deformability and its underlying mechanisms in regional venous blood following coronary occlu sion in dogs. Proceedings of Beijing satellite of the 8th International Co ngress of Biorheology,Peking University Press, 1992， 226～229.74.Qin FZ, Zhao RR, Zhang WF, Zhao ZQ, Zhou YY. Influence of reduced eryt hrocyte deformability on coronary hemodynamics,cardiac function and myocardial u ltrastructure in dogs. Proceedings of Beijing satellite of the 8th Interna tional Congress of Biorheology,Peking University Press, 1992， 182～185. 75.Dun W, Zhao RR, Liang Y， Wu BW. Effects of dopexamine hydrochlori de on calcium channels in isolated guinea pig ventricular myocytes. Meth Find Ex p Clin Pharmacol, 1996， 18(6):353～357.76.Qin FZ, Wang WZ, Zhao RR. Effects of dopexamine on heart function of i solated hypoxic rabbit heart and in comparison with fenoldopam and procaterol. A cta Pharmacologica Sinica, 1996, 17(5):435～438.77.Jin XH, Wang WZ, Zhao RR. Comparison of the characteristics and densit y of dopamine l receptors in membranes from different arteries using ［3H］ SC H23390 binding. Meth Find Exp Clin Pharmacol, 1995, 17(7):455～461.78.Zhang H, Qiao ZD, Zhao YJ, Zhao RR. Transcription of dopamine D1A rece ptor mRNAs in rat heart. Meth Find Exp Clin Pharmacol, 1996，18(3):183～187.79.Zhu L, Wang WZ, Jin XH, Zhao RR, Ake Hjalmarso,Michael LX Fu. Immunocy tochemical studies of M2 muscarinic receptors in guinea pig atria and ventricl es using anti-peptide antibodies.Blood Pressure, 1996, 5(suppl 3): 19～21.80.Wang WZ, Zhao RR, Wu BW, Jin XH, Lin Zhu,Ake Hjalmarson,Michael LX Fu. Effects of anti-peptide antibodies againsthuman M2 muscarinic receptors on c ardiac function in rats in vivo.Blood Pressure, 1996, 5(suppl 3): 25～27.81.Wang WZ, Zhao RR, Zhu L, Jin XH, Ake Hjalmarson,Michael LX Fu. Effects of anti-peptide antibodies aginst human M2 muscarinic receptors on the cAMP genrating system in guinea pig ventricles.Blood Pressure, 1996， 5(suppl 3): 33 ～24.82.Zhao RR, Wang WZ, Wu BW, Ake hjalmarson,Michael LX Fu. Effects of anti -peptide antibodies against the second extracellular loop of human M2 muscari nic receptors on transmembrane potentialsand currents in guinea pig ventricular myocytes.Mol Cell Biochem, 1996， 163/164; 185～193.83.马季骅，梁惠云，张培华，赵荣瑞.高钾时心室肌电-机械交替活动的分析.中国 病理生理杂志，1997，13(1)：38～42.84.Zhang M,Zhang H,Zhao YJ,Zhao RR. Transcription of dopamine D1A recepto r mRNA in rat kidney.(Abstract).Chin J Med, 1997， 110(9):700.85.张琳，刘慧荣，赵荣瑞，刘力生. 扩张型心肌病抗心肌β1与M2受体自身抗 体的研究.中华心血管病杂志，1998，26(1)：15～17.86.张麟，张健，陶贞寅，宋艳丽，赵荣瑞，刘力生. 高血压性心脏病抗G-蛋白耦 联受体自身抗体的初步研究.高血压杂志，1998，6(1)：5～8.87.秦富忠，张炜芳，赵荣瑞，陈建鸣. 多培沙明对心肌缺血时大鼠心脏血液动力学 的影响及其与非诺多泮和丙卡妥罗效应的比较.药学学报，1998，33(2)：106～110. 88.赵荣瑞.外周多巴胺受体研究进展.复旦神经生物学讲座，1998，XIV：27～38.[ ZK) 89.张梅，张红，赵荣瑞.老年大鼠心脏及肾脏血管紧张素AT1受体mRNA水平与受体密 度的变化.中华老年医学杂志，1998，17(5)：303～306.90.张炜芳，支建明，郭薇，赵荣瑞，金国章.左旋千金藤啶碱对外周血管多巴胺DA l和DA2受体亚型的作用.药学学报，1998，33(10)：721～726.91.Dun W,Zhao RR,Wu BW. 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Insulin-like growth factor Ⅰ inhibits c ardiomyocyte apoptosis and the underlying signal transduction pathways. Meth Fin d Exp Clin Pharmac, 2000, 22(8):601～607.

苄基四氢巴马汀对豚鼠心肌动作电位的影响

苄基四氢巴马汀(Benzyltetrahydropalmatine,BTHP)是从罂粟科植物延胡索(Corydalis ambigua(Pall)cham.et Schlecht)中提取的异喹啉类生物碱的衍生物.整体实验表明其具有抗多种心律失常的作用,降低自律性、减慢频率[1,2].为明确BTHP的抗心律失常机制,本实验利用标准微电极技术[3]观察了BTHP对豚鼠乳头状肌动作电位(AP)的影响,并进一步采用全细胞膜片钳技术[4]研究了BTHP对豚鼠单个心室肌细胞AP的作用.

Objective The autonomic nervous system plays a key role in regulating cardiac function by modifying heart rate, contractility and impulse. The parasympathetic neurotransmitter acetyl-choline and muscarinic agonist carbachol (Cch) inhibit excitation-contraction coupling in cardiac ventricular myocytes. Muscarinic agonists suppress adenylyl cyclase (AC) acitivity and,by reducing activation of the cAMP/protein kinase A (PKA)cascade, inhibit the L-type Ca2+ current (ICa(L) ). They also increase the content of cGMP by stimulating guanylyl cyclase (GC) activity. The role of nitric oxide (NO)/cGMP in muscarinic inhibition has undergone considerable scrutiny. The role of the NO/cGMP pathway in the inhibition of ICa(L) by Cch was examined in guinea-pig ventricular myocytes.

Troglitazone, a member of the insulin-sensitizing thiazolidinediones, was shown to suppress voltage-dependent L-type calcium currents (ICa, L) in vascular smooth muscle cells. The present study was aimed to investigate whether troglitazone may inhibit ICa, L in rat cardiac ventricular myocytes and whether the extent of troglitazone-induced inhibition of the current may be different between normal and streptozotocin (STZ)-induced diabetic rats. Whole-cell patch-clamp techniques were applied in single rat ventricular myocytes. Troglitazone reduced the amplitude of ICa, L in a concentration-dependent manner in both normal and diabetic myocytes. However, the percent inhibition of ICa, L by troglitazone in concentration of 10-5mol/L measured at a holding potential of -50 mV was significantly greater in myocytes isolated from STZ-induced diabetic rats than in control rats (87%±8% vs 47%±5%, P＜0.005), without difference in voltage-dependency of the inhibition. These findings demonstrate that troglitazone-induced inhibition of ICa, L is augmented in STZ-induced diabetic cardiac ventricular myocytes, thus possibly playing a role in preventing intracellular calcium overload.

AIM:To investigate whether KCNE 2 participates in the development of pathological hypertrophy .METHODS:Bidirectional ma-nipulations of KCNE2 expression were performed by adenoviral overexpression of KCNE 2 or knockdown of KCNE2 with RNA interfer-ence in PE-induced neonatal rat ventricular myocytes .Then overexpression of KCNE 2 in mouse model of left ventricular hypertrophy in-duced by transverse aortic constriction (TAC) by ultrasound microbubble-mediated gene transfer were used to detect the therapeutic function of KCNE2 in the development of hypertrophy .RESULTS:KCNE2 expression was significantly decreased in PE-induced hy-pertrophic cardiomyocytes and in hypertrophic hearts produced by TAC .Knockdown of KCNE2 in cardiomyocytes reproduced hypertro-phy, whereas overexpression of KCNE2 attenuated PE-induced cardiomyocyte hypertrophy .Knockdown of KCNE2 increased calcineurin activity and nuclear NFAT protein level , and pretreatment with nifedipine or FK 506 attenuated decreased KCNE 2-induced cardiomyo-cyte hypertrophy .Overexpression of KCNE 2 in heart by ultrasound microbubble-mediated gene transfer suppressed the development of hypertrophy and activation of calcineurin-NFAT and MAPK pathways in TAC mice .CONCLUSION:These findings demonstrate that cardiac KCNE2 expression is decreased and contributes to the development of hypertrophy via activation of calcineurin -NFAT and
MAPK pathways .

AIM:To investigate the regulation mechanism for insufficient KChIP 2 expression induces Ito,f downregulation and arrhythmogene-sis in cardiac hypertrophy .METHODS:Bidirectional manipulations of MG 53 expression were performed by adenoviral overexpression of MG53 or knockdown of MG53 with RNA interference in neonatal rat ventricular myocytes with or without PE stimulation .Ito,f was re-corded with patch clamp in whole-cell mode 48 h after adenoviral transfection .Then the WT or MG53 knockout ( MG53 -/-) mouse model of left ventricular hypertrophy induced by transverse aortic constriction ( TAC) were used to detect the susceptibility to ventricu-lar arrhythmia.RESULTS: Here, we show muscle-specific MG53 regulates KChIP2 expression and Ito,f densities, where they are downregulated in hearts from MG53 knockout mice and MG53 knockdown rat cardiomyocytes , but upregulated in MG53 overexpressed cells.MG53 expression is decreased in phenylephrine ( PE)-induced cardiomyocyte hypertrophy and restoration of MG 53 rescues PE-induced downregulation of KChIP2 and Ito,f.Furthermore, MG53 is decreased in a mouse model of hypertrophy induced by transverse aortic constriction and ablation of MG 53 increases the susceptibility to ventricular arrhythmia by exaggerating Ito,f remodeling.CON-CLUSION:These findings establish MG53 as a novel regulator of Ito,f and its central role in arrhythmogenesis in hypertrophy .