亚硒酸钠诱导人急性早幼粒细胞白血病细胞株NB4细胞氧化应激和细胞凋亡

目的研究亚硒酸钠诱导NB4细胞的氧化应激和细胞凋亡。方法MTT比色法检测亚硒酸钠对NB4细胞的生长抑制;用形态学、DNA琼脂糖电泳和流式细胞术研究亚硒酸钠诱导NB4细胞凋亡的作用;用化学发光法和比色法研究亚硒酸钠对NB4细胞内氧化应激的影响。 结果亚硒酸钠可以时间和剂量依赖性地抑制NB4细胞生长和诱导NB4细胞凋亡。亚硒酸钠(≥5 μmol·L^-1)提高了NB4细胞内ROS水平,同时伴有细胞内还原型谷胱甘肽含量下降,而抗氧化剂NAC可抑制亚硒酸钠诱导的NB4细胞氧化应激和细胞凋亡。结论亚硒酸钠诱导NB4细胞氧化应激可能是其诱导NB4细胞凋亡的重要机理。     

低剂量的硒与镉联合作用对大鼠肝细胞DNA损伤的影响

目的 研究低剂量的亚硒酸钠和氯化镉联合作用对离体大鼠肝细胞DNA损伤的影响。方法 在2．185、4．375和8．750μmol／L的剂量条件下，亚硒酸钠和氯化镉联合作用，用单细胞凝胶电泳检测大鼠肝细胞DNA损伤。结果 2．185μmol／L的亚硒酸钠对2．185μmol／L的氯化镉引起的DNA损伤拮抗作用不明显，但有拮抗作用的趋势；4．375μmol／L亚硒酸钠对4．375μmol／L氯化镉引起的DNA损伤有明显的拈抗作用；而在8．750μmol／L的剂量下，亚硒酸钠与氯化镉存在相互拈抗的关系。结论 在硒和镉对大鼠肝细胞DNA损伤的联合作用中，较低剂量的亚硒酸钠对氯化镉没有拮抗作用，而在一定的剂量条件下，亚硒酸钠和氯化镉存在着相互拮抗的关系。     

亚硒酸钠诱发大鼠胚胎中脑神经细胞凋亡的观察

目的：研究亚硒酸钠对大鼠胚胎中脑神经细胞凋亡的影响。并探讨其中可能的机制。方法：采用原代培养的大鼠胚胎中脑神经细胞,加入不同浓度的亚硒酸钠（1、5、10、20μmol/L),观察亚硒酸钠对神经细胞凋亡的影响,用透射电镜观察神经细胞超微结构的变化,流式细胞仪分析法检测DNA含量及凋亡细胞百分率。结果高浓度的亚硒酸钠（≥10μmol/L）会导致神经细胞凋亡,并呈剂量依赖性,10μmol/L的亚硒酸钠作用的神经细胞导现出典型的凋亡形态学改变,且凋亡细胞百分率达13．4％。结论：高浓度的硒可通过激发生氧自由基和调节有关调节基因（P53）的活性等多种途径诱发神经细胞凋亡。     

胰岛素与硒联合应用治疗糖尿病大鼠的可行性分析

目的确定胰岛素和硒联合应用治疗糖尿病大鼠的可行性。方法建立糖尿病模型,胰岛素皮下注射给药,亚硒酸钠口服给药。胰岛素和亚硒酸钠分别设计2个剂量(胰岛素:1和0.5u.kg-1;亚硒酸钠:180和60μg.kg-1)。按2因素2水平的L4(22),运用正交实验设计确定胰岛素和硒联合应用的合理配比剂量。结果胰岛素与亚硒酸钠对糖尿病大鼠血糖的降低作用存在相互影响,胰岛素和硒联合应用的合理配比剂量是1u.kg-1∶180μg.kg-1。结论胰岛素和硒联合应用在降低血糖方面明显优于单用相同剂量的胰岛素或亚硒酸钠,联合用药(胰岛素+硒)发挥了协同作用。     

亚硒酸钠对HL—60细胞的自由基产生和清除的影响

本文研究亚硒酸钠对HL－60细胞生长增殖和自由基的产生与清除的影响，结果表明，亚硒酸钠显著抑制HL－60细胞的生长增殖；亚硒酸钠短期作用对细胞内脂质过氧化物（MDA）含量无明显影响，而过氧化氢酶（CAT）活性明显降低,超氧化物歧化酶（SOD）活性明显增高,并讨论其与抑瘤作用的关系．     

亚硒酸钠联合泼尼松治疗亚急性甲状腺炎临床观察

目的:探讨亚硒酸钠联合泼尼松对亚急性甲状腺炎患者的影响.方法:对2004年9月-2008年8月在本院诊治的78例亚甲炎患者进行随机对照前瞻性研究.对照组有2例失访,37例完成观察,治疗组39例.两组均予以泼尼松治疗(30 mg/d),治疗组加服亚硒酸钠,总疗程8周左右.结果:经过8周治疗,第2、4周亚硒酸钠组的血沉低于对照组(P＜0.05),亚硒酸钠组2 h、6 h和24 h吸碘率的高于对照组(P＜0.01),而复发率低于对照组(P＜0.05).结论:亚硒酸钠可以缩短亚急性甲状腺炎病程,减少复发率.     

让合理、安全用药知识走进千家万户(四十)

正(接上期)科学补硒方法是:A、人工补硒:摄取人工添加的各类补硒产品主要分为无机硒和有机硒两类,无机硒主要为亚硒酸钠,国外多用于饲料使用,有很大的毒素,已处于淘汰的边缘。有机硒与亚硒酸钠等无机硒相比,具有食用安全、无毒副作用、吸收利用率高、营养价值高等优点。有机硒的种类很多,如硒酵母、硒蛋、富硒藻类、富硒蘑菇和硒麦芽等,其中麦芽硒是目前有机硒发展的最高阶段,比     

植物甲基源硒和传统补硒制剂的代谢差异

<正>传统补硒制剂包括亚硒酸钠、硒酸钠、硒半胱氨酸和硒蛋氨酸等。它们的共同特点是:(1)在人体内发挥预防作用的活性形态是硒蛋白;(2)在体内需要经多步复杂的代谢过程插入硒蛋白。     

亚硒酸钠通过Keap1/Nrf2/ARE信号通路诱导人肺腺癌A549细胞凋亡

目的探究亚硒酸钠诱导人肺腺癌A549细胞凋亡的作用及可能的分子机制。方法 MTT法检测不同浓度亚硒酸钠对人肺腺癌A549细胞的抑制增殖率;倒置荧光显微镜观察细胞经亚硒酸钠处理后的形态学改变;流式细胞术检测细胞凋亡率;激光共聚焦观察活性氧荧光强度;多功能酶标仪测定氧化应激参数含量;Western blot检测Keap1/Nrf2/ARE信号通路蛋白的表达,以及Nrf2在细胞质和细胞核中的蛋白表达情况。结果亚硒酸钠剂量依赖性地抑制人肺腺癌A549细胞增殖,亚硒酸钠作用于人肺腺癌A549细胞24 h后,通过Hoechst 33342固定和流式细胞术分析,细胞凋亡率明显增加;亚硒酸钠可使活性氧和丙二醛水平明显升高,还原型谷胱甘肽和超氧化物歧化酶含量明显下降;同时亚硒酸钠能够下调Keap1、Nrf2和HO-1蛋白的表达,并且抑制Nrf2发生核位移。结论亚硒酸钠通过抑制人肺腺癌A549细胞增殖,诱导细胞凋亡,调节细胞内的氧化应激反应,调控Keap1/Nrf2/ARE抗氧化信号通路,从而促进肿瘤细胞凋亡。     

正交设计研究多贝斯和硒的抗血小板血栓作用

目的　研究多贝斯与硒 2种药物联合应用抗血小板血栓形成的作用 ,寻求合用的最佳组方剂量。方法　采用 2因素 3水平 [L9(34 ) ]的正交设计 ,观察药物对大鼠动 -静脉旁路血小板血栓形成的影响 ,用 SPSS软件统计实验结果。结果　在抑制血栓形成方面 ,多贝斯的作用强于亚硒酸钠 ;多贝斯的低剂量 (6 3mg.kg-1)作用最强 ;亚硒酸钠的中剂量 (0 .1mg.kg-1)作用最强。最佳搭配应为多贝斯低剂量加亚硒酸钠中剂量。结论　多贝斯与亚硒酸钠的交互作用有统计学意义 ,两药合用在抗血栓形成中为拮抗作用 ,故不宜合用     

亚硒酸钠对豚鼠及家兔心脏自发电活动的影响

Effects of Na₂Seo₃ on the spontaneous electric activity in guinea pig ventricular muscle induced by BaCl₂ and on the rabbit sinoatrial node were observed using glass microelectrode technique. The results showed that addition of 0.6mM Na₂Seo₃ caused the barium-induced spontaneous electric activity in ventricular muscle to decrease or disappear. When sinoatrial node cells were exposed to 0.9mM Na₂Seo₃, their APA, SPo and SP₄ decreased and APD₉₀, SCL were prolonged. While, when the concentration of Na₂Seo₃ was increased to 1.2raM, the AP of sinoatrial node cells disappeared. The results indicate that Na₂Seo₃ may suppress the spontaneous electric activity.     

异紫堇啡碱对家兔窦房结及豚鼠心室肌动作电位的作用

用细胞内固定微电极技术观察了异紫堇啡碱(isocorydine)对家兔窦房结电活动、豚鼠心室肌动作电位及Ba²⁺诱发的豚鼠心室肌自发电活动的作用。结果表明,异紫堇啡碱能使窦房结细胞APA,SP₀,SP₄减小、APD₉₀延长、自律性降低。3 μM异紫堇啡碱能使心室肌细胞的APD₅₀,APD₉₀和ERP延长,300μM异紫堇啡碱则使心室肌细胞APD₅₀和APD₉₀缩短,但不缩短ERP,使ERP相对延长。300μM异紫茧啡碱亦能明显抑制Ba²⁺诱发的心室肌自发电活动。     

Cardiac electrophysiological actions of captopril: lack of direct antiarrhythmic effects.

1. Standard microelectrode techniques were used to study the effects of captopril (1, 10 and 100 microM) on action potentials recorded from guinea-pig ventricular cells and sinoatrial node cells. 2. Captopril had no effect on the maximum rate of depolarization (Vmax) of ventricular action potentials in cells exposed to either normal Locke solution or 'simulated ischaemic' solution (K1 11.2 mM; pH-6.4; PO2 less than 80 mmHg), nor was there any augmentation of the normal small decline in Vmax with increasing stimulation rate (range of interstimulus intervals = 2400 ms to 300 ms). 3. Captopril had no effect on the duration of ventricular action potentials, nor did it alter the shortening seen on exposure to simulated ischaemia. 4. Captopril did not alter spontaneous sinus cycle length or any recorded parameter of sinus node action potentials. 5. It is concluded that any antiarrhythmic effects observed during clinical use of captopril are most unlikely to be due to direct actions of the drug on cardiac cell membrane properties.     

On the mechanisms of cholinergic control of the sinoatrial node discharge

It has been proposed that cholinergic agonists inhibit the sinoatrial node discharge by shifting the activation range of the hyperpolarization-activated inward current If to more negative values or by increasing potassium conductance. In the former instance, cesium will potentiate the cholinergic inhibition by blocking any residual If; in the latter instance, Cs+ and Ba2+ will antagonize the inhibitory action by blocking K+ channels. The changes in discharge induced by high and low concentrations of carbachol were studied using an electrophysiologic technique in isolated guinea pig sinoatrial node perfused in vitro in the absence and presence of different concentrations of Cs+ and Ba2+. In Tyrode solution, high carbachol concentrations (0.5-2 microM) slowed the sinoatrial node by hyperpolarizing the membrane and by reducing the amplitude of diastolic depolarization; and stopped the sinoatrial node by preventing the attainment of threshold potential. Adding Cs+ (10 mM) to carbachol increased the rate in slowly discharging sinoatrial node and induced spontaneous discharge in quiescent sinoatrial node. In high [K+]o (approximately 12 mM), carbachol slowed or stopped the slow responses and adding Cs+ accelerated or induced discharge. Both in Tyode and in high [K+]o, in the presence of Cs+, carbachol did stop the sinoatrial node. In the presence of carbachol, Ba2+ (0.1 mM) accelerated or induced discharge, as Cs+ did. Atropine (1 microM) prevented both the slowing or suppression by carbachol and the acceleration of sinoatrial node by Cs+ in the presence of carbachol. Low carbachol concentrations (0.05-0.1 microM) decreased the rate to a similar extent in the absence and the presence of a low concentration of Cs+ (2 mM, which blocks If but not K+ channels), but markedly less in the presence of 0.5-0.75 mM Ba2+ (which block K+ channels but not If). We conclude that cholinergic agonists slow or stop the sinoatrial node by a shifting the membrane potential toward the more negative subsidiary pacemaker range and away from the threshold. The results with Cs+ and Ba2+ indicate that both high and low concentrations of carbachol decrease sinoatrial node discharge by activating the I(K,ACh) channels rather than by decreasing If.     

dl-四氢巴马汀对家兔窦房结和豚鼠心室肌慢反应电活动的影响

用细胞内固定微电极技术观察到dl-四氢巴马汀(THP)30～100μM使家兔窦房结细胞动作电位的振幅(APA)、零相去极化速率(SP_0)和舒张期4相去极化速率(SP_4)逐渐降低,小剂量使动作电位复极90％的时程(APD_(90))延长,大剂量使其缩短,并使心率(HR)减慢。THP 30～300μM使高K~+除极和河豚毒素(TTX)所致的豚鼠乳头状肌细胞慢反应动作电位的APA、零相最大上升速率(V_(max))逐渐降低,复极50％的时程(APD_(50))缩短。实验结果提示THP可能有钙拮抗作用。     

Pathophysiological significance of T-type Ca2+ channels: properties and functional roles of T-type Ca2+ channels in cardiac pacemaking

Calcium channels are essential for excitation-contraction coupling and pacemaker activity in cardiac myocytes. While L-type Ca(2+) channels (LCC) have been extensively studied, functional roles of T-type channels (TCC) in native cardiac myocytes are still debatable. TCC are activated at more negative membrane potentials than LCC and therefore facilitate slow diastolic depolarization in sinoatrial node cells. Recent studies showed that selective inhibition of TCC produced a marked slowing of the pacemaker rhythm, indicating that contribution of TCC to cardiac automaticity was relatively larger than what had been speculated in previous studies. To re-evaluate TCC, we measured current density and kinetics of TCC in sinoatrial node cells of various mammalian species. Current density of TCC was larger in mice and guinea pigs than in rabbit and porcine sinoatrial node cells. Interestingly, few or no obvious TCC were recorded in porcine sinoatrial node cells. Furthermore, it was demonstrated that TCC could be enhanced by several vasoactive substances, thereby increasing spontaneous firing rate of sinoatrial node cells. TCC may, at least in part, account for different heart rates among various mammalian species. In addition, TCC might be involved in physiological and/or pathophysiological modulations of the heart rate.     

Effects of 5-HT(4) receptor agonist prokinetic agents on the action potential parameters of isolated rabbit myocardium

The effects of TS-951, a novel gastrointestinal prokinetic agent with 5-HT(4) receptor agonistic action, on the action potential parameters of isolated rabbit Purkinje fiber, ventricular muscle and sinoatrial node, and on the spontaneously beating rates of isolated rabbit right atria were compared with those of cisapride. TS-951 had no effect on the action potential parameters in both rabbit Purkinje fiber and ventricular muscle preparations. However, cisapride significantly prolonged action potential duration (APD) in both preparations. Both TS-951 and cisapride produced a negative chronotropic effect in rabbit right atria; TS-951 and cisapride at 3 x 10(-5) mol/l reduced the beating rate by about 20 and 40%, respectively. In the sinoatrial node preparations, TS-951 (3 x 10(-5) mol/l) as well as cisapride (10(-6) mol/l) prolonged cycle length and APD and reduced the diastolic depolarization rate. These results indicate that TS-951 does not appear to possess electrophysiological features leading to cardiotoxicity such as QT prolongation and, thus, torsades de pointes in common with cisapride.     

Comparison of cardiovascular effects of a new calcium channel blocker AH-1058 with those of verapamil assessed in blood-perfused canine heart preparations

The cardiovascular effects of AH-1058, a novel calcium channel blocker, were examined in comparison with those of verapamil using canine isolated, blood-perfused papillary muscle, atrioventricular node, and sinoatrial node preparations. Intravenous administration of AH-1058 (20, 50, and 100 microg/kg) or verapamil (20, 50, and 100 microg/kg) to the blood-donor dog induced negative inotropic, dromotropic, and chronotropic effects and a coronary vasodilator action in cross-circulated isolated heart preparations, simultaneously inducing the same cardiac effects in the blood-donor dog. The order of potency of the effects of AH-1058 was ventricular contraction > coronary blood flow > atrioventricular conduction > sinoatrial automaticity, whereas that of verapamil was coronary blood flow > atrioventricular conduction > sinoatrial automaticity > ventricular contraction. The cardiosuppressive effects of AH-1058, especially on ventricular contraction, were slower in onset and longer lasting than those of verapamil. These results suggest that this unique cardiovascular profile of AH-1058 may become beneficial for the treatment of certain pathologic processes, in which selective inhibition of ventricular calcium channels would be essential for drug therapy.     

Electrophysiological actions of mexiletine on rabbit sinoatrial node cells

The effects of mexiletine (1-100 microM) were examined on membrane potential and current of rabbit sinoatrial node cells by means of conventional microelectrode and double microelectrode voltage clamp techniques. Mexiletine decreased, in a dose-dependent manner, the maximum rate of depolarization of the action potential and the action potential amplitude, and increased the spontaneous cycle length. The slope of the diastolic depolarization (phase 4) was also reduced. In the voltage clamp experiment, mexiletine (40-100 microM) reduced the slow inward current (Isi), the potassium outward current (IK) and the hyperpolarization-activated current (Ih). The kinetic variable of IK was not altered by the drug. These results suggest that mexiletine does not have a specific effect on a single-current system, but that relatively high concentrations of mexiletine exert an inhibitory effect on the electrical activity of the sinoatrial node cells.