植物性雌激素金雀异黄素对家兔窦房结起搏细胞的电生理效应

目的:研究植物性雌激素金雀异黄素(genistein,GST)对家兔窦房结起搏细胞的电生理效应及其作用机制.方法:应用经典玻璃微电极方法.结果:GST(10-150μmol/L)不仅以剂量依赖性方式抑制窦房结起搏细胞的零相最大上升速度(V_(max)),舒张期除极速度(VDD),起搏放电频率(RPF)和动作电位幅度(APA),而且延长复极化90％时间(APD_(90)).提高灌流液中钙离子浓度以及应用L型钙通道开放剂Bay K8644(0.5μmol/L)均可逆转GST对起搏细胞的上述电生理效应,但NO合酶阻断剂L-NAME(1 mmol/L)对GST的效应并无影响.结论:GST对家兔窦房结具有负性变时作用,并可延长复极化时程.这些效应可能与其抑制钙离子内流及钾离子外流有关.     

内源性腺苷和K_(ATP)通道介导缺氧窦房结起搏细胞的电生理效应(英文)

目的:观察腺苷脱氨酶(ADase),8-苯茶碱(8-PT)和格列苯脲(Gli)在豚鼠缺氧窦房结起搏细胞的电生理效应.方法:以充有100％氮和无糖的K-H液灌流豚鼠窦房结20 min引起其缺氧.用玻璃微电极技术记录起搏细胞的MDP,APA,APD_(90),V_(max),RPF和VDD等动作电位参数.结果:缺氧增加起搏细胞APA,MDP和V_(max),但减小VDD和RPF.Adase 10 U·L~(-1),8-PT 0.1 μmol·L~(-1)和Gli10 μmol·L~(-1)明显缓解缺氧引起的电生理效应. 结论:内源性腺苷和KATp通道在缺氧所致窦房结起搏细胞电生理效应中起重要作用.     

白藜芦醇对家兔窦房结起搏细胞的电生理效应(英文)

目的为探讨白藜芦醇是否能成为抗心律失常药,研究了其对窦房结起搏细胞的电生理效应。方法应用细胞内微电极方法记录家兔窦房结起搏细胞的动作电位。结果白藜芦醇(30~120μmol.L-1)显著降低窦房结起搏细胞的动作电位幅度、零相最大上升速率(Vmax)、舒张期除极速率和起搏放电频率。而对最大舒张期电位和90%复极化的时间无明显作用。预先应用L型钙通道开放剂Bay-K-8644(0.5μmol.L-1)灌流窦房结10 min可阻断白藜芦醇(60μmol.L-1)对起搏细胞的上述电生理效应。而应用超极化激活电流阻断剂氯化铯(2 mmol.L-1)加钾通道阻断剂四乙铵(20 mmol.L-1)或应用一氧化氮(NO)合酶阻断剂-LNAME(0.5 mmol.L-1)灌流窦房结标本10min对白藜芦醇(60μmol.L-1)的电生理效应没有明显影响。结论白藜芦醇能抑制家兔窦房结起搏细胞的自发活动,此效应可能与其通过非NO依赖性途径抑制钙离子内流有关。     

莫索尼定对兔窦房结起搏细胞的电生理效应(英文)

目的　研究莫索尼定 (Mox)对窦房结起搏细胞是否具有电生理作用及其相关受体以探讨Mox治疗实验性心律不齐的机理。方法　利用细胞内微电极技术记录窦房结细胞AP。结果　Mox(0 .3～ 3mmol·L- 1)浓度依赖性地降低AP的舒张期除极速率 (VDD) ,减慢自发搏动速率 (RPF) ,延长AP复极达 5 0 %及 90 %的时程 (APD50 和APD90 )。 1和 3mmol·L- 1Mox还明显增大最大舒张电位 (MDP)的绝对值。预先灌流α2 受体拮抗剂育亨宾 (1.0 μmol·L- 1,2 0min)取消Mox降低VDD ,延长APD50 和APD90 的作用 ;拮抗较低浓度Mox降低RPF和增大MDP的作用。育亨宾处理标本后 ,Mox显著增加AP幅度和最大除极速率。结论　Mox延长兔窦房结起搏细胞动作电位APD50 和APD90 以及降低VDD的作用主要由α2 受体中介。Mox增大MDP绝对值和减慢RPF的作用则与α2 受体部分相关     

辣椒素对人心房肌的电生理效应(英文)

目的　研究辣椒素对人心房肌的电生理效应及其作用机制。方法　应用经典玻璃微电极方法记录人心房肌特殊细胞的动作电位。结果　辣椒素(1～ 30 μmol·L- 1)浓度依赖性地抑制人心房肌纤维的动作电位幅值 ,0期最大除极速率 ,舒张期 (4相 )除极化速率和起搏细胞放电频率 ,此外还缩短 90 %动作电位时程。应用L 型钙通道开放剂BayK86 44(0 .5 μmol·L- 1)可拮抗辣椒素对人心房肌纤维的上述电生理效应 ,但辣椒素受体竞争性抑制剂cap sazepine(10 μmol·L- 1)对辣椒素的效应并无影响。结论　辣椒素对人心房肌具有负性变时作用 ,并可缩短复极化时程。这些效应可能与其抑制钙离子内流有关。     

中华眼镜蛇全毒对离体大鼠窦房结和乳头肌的电生理效应

用玻璃微电极和心脏活体灌流技术,观察到中华眼镜蛇全毒(1μg/ml)在5min内使离体大鼠窦房结起搏动作电位振幅(APA)降低48.1±SD5.8mV,最大舒张期电位(MDP)衰减-52.0±3.0mV,并最好发生“非可逆性去极化”。舒张期4相去极化速率(RP4D)减慢57.1±SD3.5 mV/s,并产生不规则的类“后电位振荡”现象,导致4相去极化和复极化的紊乱,窦性周长(P)亦延长150±SD70ms。离体大鼠乳头肌经蛇毒1μg/ml灌流,3min内即呈现剧烈的负变力效应,等长峰张力(PCF)衰减了12.5±SD 2.8mm。上述结果提示,中华眼镜蛇全毒中可能含有类“心脏毒素”组分。     

新鱼腥草素钠抑制胰腺癌 Panc-1细胞恶性生物学行为及其作用机制研究

目的探究新鱼腥草素钠(SNH)对胰腺癌 Panc-1细胞增殖、侵袭及迁移能力的影响及其潜在作用机制。方法自 2023年 3月至 2024年 2月,取对数期人胰腺癌 Panc-1细胞,分为对照组(无菌双蒸水)、各不同梯度 SNH处理组( 100 μmol/L组、 200 μmol/L组、 400 μmol/L组、 600 μmol/L组及 800 μmol/L组)。细胞计数试剂( CCK-8)实验检测 Panc-1细胞活率;细胞划痕及 Transwell实验分别检测细胞迁移及侵袭能力;实时荧光定量聚合酶链式反应( qRT-PCR)检测细胞基因水平的变化。蛋白质印迹法检测凋亡蛋白胱天蛋白酶 -3(caspase-3)、多聚二磷酸腺苷核糖聚合酶( PARP)及上皮间质转化( EMT)相关蛋白神经钙黏素( N-cadherin,CDH)、闭合蛋白( occludin,OCLN)的表达。结果 CCK-8实验结果显示, 24 h时, 100、200及 400 μmol/L组细胞活率与对照组相比差异无统计学意义; 600、800 μmol/L组显著降低( P=0.002,P<0.001); 48、72 h时, 100、200 μmol/L组细胞活率未见降低, 400、600、800 μmol/L组明显下降( P<0.001),各组 48 h细胞活率分别为( 62.51±9.59)%、(36.94±5.06)%及( 17.94±0.56)%,72 h降至( 46.00±3.04)%、(22.93±4.75)%及( 5.80±0.42)%。细胞划痕结果显示, 100 μmol/L组 24 h细胞迁移率即下降(P<0.05)48 h迁移率( 4.37±1.92)%及 72 h迁移率( 3.75±2.47)%均明显低于对照组( P<0.01); 200 μmol/L组细胞迁移率同样下降, 72 h率为( 6.25±5.16)%;Transwell实验结果显示,与对照组相比, 24 h时 200、400 μmol/L组侵袭细胞数显著减少(均 P<0.001)迁移; qRT-PCR结果显示, 400 μmol/L组 CDH2基因表达下调( P<0.05),OCLN表达上调( P<0.05);蛋白质印迹法检测, 400 μmol/L组 caspase-3、PARP表达降低( P<0.05)cleaved caspase-3升高( P<0.05)。 200、400 μmol/L组 CDH表达降低( P<0.001), OCLN升高( P<0.001)。结论 SNH抑制胰腺癌细胞的增殖、迁移和侵袭,可能与 SNH促进细胞凋亡,抑制 EMT进程有关。     

胍丁胺对兔窦房结起搏细胞的电生理效应(英文)

目的:研究胍丁胺(Agm)对兔窦房结起搏细胞的电生理效应及其作用机制。方法:应用玻璃微电极方法。结果:Agm不仅能剂量依赖地抑制兔窦房结起搏细胞的V_(max),APA和VDD,RPF;而且能延长APD_(90);idazoxan能明显抑制Agm的电生理效应;而L-NAME不能影响Agm的电生理效应;提高灌流液中的Ca~(2 )浓度可对抗Agm的作用;ATP-敏感性钾通道开放剂(lemakalim)可部分拮抗Agm延长APD_(90)的作用。结论:Agm对窦房结的电生理效应由肾上腺素能α-受体和咪唑啉受体介导,并与Ca~(2 )内流和K~ 外流减少有关。     

多普勒超声心肌活动指数评价心脏整体功能

目的探讨超声多普勒检测评价心肌活动指数(Tei指数)的临床价值。方法对10头猪进行快速右心室起搏,分别于起搏前及起搏3周关闭起搏器后进行多普勒超声心动图检查,测定左室舒张末期内径(LVDd)、收缩末期内径(LVDs)、等容舒张时间(IVRT)、等容收缩时间(IVCT)和射血时间(ET),计算射血分数(EF)、每搏输出量、每分输出量和左室心肌活动指数。结果起搏后LVDd(4.66±0.16)cm、LVDs(3.73±0.17)cm较起搏前LVDd(3.80±0.12)cm、LVDs(2.20±0.14)cm明显增大,(P<0.01);起搏后IVRT(0.07±0.01)sI、VCT(0.05±0.01)s,较起搏前IVRT(0.05±0.01)s、IVCT(0.04±0.01)s延长,(P<0.01);起搏后ET(0.18±0.02)s较起搏前(0.20±0.02)s缩短;起搏后MPI(0.69±0.16)较起搏前(0.47±0.07)明显延长。结论心肌活动指数能简便、敏感、综合评价心脏的整体收缩舒张功能。     

腺苷三磷酸通过P1受体影响兔窦房结起搏细胞电生理活动(英文)

目的:研究腺苷三磷酸(ATP)对兔离体窦房结起搏细胞动作电位的作用,分析相关受体。方法:利用细胞内微电极技术记录兔离体窦房结细胞跨膜电位。结果:ATP 0.1-3.0mmol/L浓度依赖性减慢窦房结自发搏动速率16％-43％,降低舒张期除极速率33％-67％,增大动作电位幅值6％9％,加快最大除极速率30％-76％,APD_(50)和APD_(90)分别缩短7％-12％和6.3％-9％,等浓度ATP、腺苷二磷酸(ADP)和腺苷(Ado)的效应相比时,各组间无显著性差异,尿苷三磷酸(UTP)和α,β-meATP对动作电位各参数均无影响,P1受体拮抗剂氨茶碱(0.1mmol/L)显著拮抗ATP和Ado的作用(P<0.05),且拮抗程度相同,P2受体拮抗剂反应兰2 (0.05mmol/L)不影响ATP的作用(P<0.05)。结论:兔窦房结不存在功能性P2X,和P2Y_2受体,ATP对兔窦房结的作用主要通过其降解产物Ado,由P1受体介导而发挥。     

Capsaicin facilitates carotid sinus baroreceptor activity in anesthetized rats

AIM: To study the effect of capsaicin on carotid sinus baroreceptor activity (CBA). METHODS: The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid sinus baroreceptor were measured by recording sinus nerve afferent discharge in anesthetized rats with perfused isolated carotid sinus. RESULTS: Low-concentration of capsaicin (0.2 μmol/L) had no significant effect on CBA, while perfusion of the isolated carotid sinus with middle-concentration of capsaicin (1 μmol/L) could shift FCCB to the left and upward, with peak slope (PS) increased from (2.47 %±0.14 %)/mmHg to (2.88 %±0.10 %)/mmHg (P<0.05) and peak integral value of carotid sinus nerve discharge (PIV) enhanced from 211 %±5 % to 238 %±6 % (P<0.01). The threshold pressure (TP) and saturation pressure (SP) were significantly decreased from 68.0±1.1 to 62.7±1.0 mmHg (P<0.01) and from 171.0±1.6 to 165.0±0.6 mmHg (P<0.01). By perfusing with high-concentration of capsaicin (5μmol/L), FCCB was shi     

关附乙酯对兔窦房结起搏细胞的作用

目的:研究关附乙酯(DGFA)对窦房结起搏细胞电生理学的影响.方法:采用细胞内微电极技术记录家兔窦房结动作电位(AP)参数.结果:DGFA不仅能够减慢自主性激发频率(SFF),平均复极化速率(MRR),舒张期除极化速率(RDD),而且以剂量依赖性方式延长窦房结舒张期间隔(DI)和动作电位时程(APD).此外,DGFA显著降低除极化最大速率(MRD),并伴有动作电位幅度(APA)的轻微下降,对最大舒张电位(MDP)无显著作用.DGFA降低自主性激发频率的作用不受阿托品(0.05 mg/L)的影响.结论:DGFA这些作用可能是通过减少钙离于内流及钾离子外流产生的,而非阻断M受体.     

Electrophysiological effects of lidocaine, l-chlorpheniramine, and bepridil on rabbit sinus node pacemaker cells

We compared the electrophysiological effects of lidocaine, l-chlorpheniramine, and bepridil on rabbit sinus node pacemaker cells. Only bepridil (0.25-2.0 mg/L) caused a marked reduction in the automaticity of the sinus node. Action potential amplitude, overshoot, and maximum rate of depolarization of phase O (MRD) were all reduced in a dose-dependent manner by bepridil. Decreases in maximum diastolic potential (MDP) and take-off potential were also observed, the former falling to approximately -40 mV when automaticity ceased. On the other hand, lidocaine (12-48 mg/L) depressed the upstroke of the action potential without significantly affecting MDP or take-off potential. The action potential duration was also prolonged at these concentrations. Both MDP and take-off potential were markedly reduced by l-chlorpheniramine (2.9-11.6 mg/L) and these changes were accompanied by reductions in amplitude, overshoot, and MRD of the action potential. A prolongation of the action potential duration was also observed. Pacing the sinus node preparations at a frequency of 4.5 Hz depressed the upstroke of the action potential and led to postoverdrive suppression. l-Chlorpheniramine abolished the postoverdrive suppression, whereas in the presence of lidocaine and bepridil a marked reduction and alternation in action potential amplitude occurred on pacing which made the accurate assessment of sinus node recovery time impossible.     

Effect of resveratrol on L-type calcium current in rat ventricular myocytes

AIM: To study the effect of resveratrol on L-type calcium current (I(Ca-L)) in isolated rat ventricular myocytes and the mechanisms underlying these effects. METHODS: I(Ca-L) was examined in isolated single rat ventricular myocytes by using the whole cell patch-clamp recording technique. RESULTS: Resveratrol (10-40 micromol/L) reduced the peak amplitude of I(Ca-L) and shifted the current-voltage (I-V) curve upwards in a concentration-dependent manner. Resveratrol (10, 20, 40 micromol/L) decreased the peak amplitude of I(Ca-L) from -14.2+/-1.5 pA/pF to -10.5+/-1.5 pA/pF (P<0.05), -7.5+/-2.4 pA/pF (P<0.01), and -5.2+/-1.2 pA/pF (P<0.01), respectively. Resveratrol (40 micromol/L) shifted the steady-state activation curve of I(Ca-L) to the right and changed the half-activation potential (V0.5) from -19.4+/-0.4 mV to -15.4+/-1.9 mV (P<0.05). Resveratrol at a concentration of 40 micromol/L did not affect the steady-state inactivation curve of I(Ca-L), but did markedly shift the time-dependent recovery curve of I(Ca-L) to the right, and slow down the recovery of I(Ca-L) from inactivation. Sodium orthovanadate (Na(3)VO(4); 1 mmol/L), a potent inhibitor of tyrosine phosphatase, significantly inhibited the effects of resveratrol (P<0.01). CONCLUSION: Resveratrol inhibited I(Ca-L) mainly by inhibiting the activation of L-type calcium channels and slowing down the recovery of L-type calcium channels from inactivation. This inhibitory effect of resveratrol was mediated by the inhibition of protein tyrosine kinase in rat ventricular myocytes.     

Effects of diltiazem on the electrophysiological properties of cat ventricular muscle fibers during experimentally induced right ventricular systolic hypertension

The electrophysiological effects of diltiazem were studied in right ventricular muscle fibers from normal cats and cats with experimentally induced right ventricular systolic hypertension (RVSH). Two types of action potential (AP) abnormalities were observed in preparations from cats with RVSH: Type I cells, found in most areas of the right ventricular free wall, demonstrated reduced maximum diastolic potential (MDP) (-64.4 mV) and Vmax (89.6 V/s) while Type II cells showed a "slow response" AP configuration (MDP, -48.8 mV; AP amplitude, 48.9 mV; AP duration at 50% repolarization, 47.5 ms; AP duration at 90% repolarization, 90.2 ms; Vmax, 13.1 V/s) and were often monitored near the tricuspid valve. Diltiazem (2.2 X 10(-7) and 2.2 X 10(-6) M) had no effect on MDP of normal, Type I, or Type II cells. Diltiazem at 2.2 X 10(-6) M significantly reduced AP amplitude and Vmax of both Type I and normal cells. In contrast, even at 2.2 X 10(-7) M, diltiazem significantly reduced AP amplitude and Vmax of the Type II cells. Diltiazem, 2.2 X 10(-6) M, would often abolish AP of Type II cells, while Type I cells were more sensitive to tetrodotoxin. AP duration of normal cells was unaffected by diltiazem while that of Type I and II cells was significantly shortened.     

磷酸羟基喹哌对豚鼠心室肌和家兔窦房结细胞慢反应电活动的影响

为进一步研究HPQP抗心律失常的机理,本实验采用细胞内固定微电极技术,观察到该药在30μmol/L可降低高钾除极化心肌动作电位APA和V_(max);对V_(max)呈频率依赖性抑制作用;抑制钡诱发的心室肌自发电活动;对家兔窦房结优势起搏细胞的V_(max)和APA均有抑制,延长APD_(50)和APD_(100),降低四相除极斜率。以上结果均表明该药对钙通道有阻滞作用。     

双苯氟嗪对豚鼠心室肌细胞L-钙电流的影响

目的:观察双苯氟嗪(Dip)对豚鼠心室肌细胞L-型钙电流(I_(Ca-L))的影响。方法:酶解法制备单个心室肌细胞。应用全细胞膜片箝技术记录豚鼠单个心室肌细胞钙电流。结果:在0.3-30μmol/L范围内,Dip可浓度依赖性地降低电压依赖性激活I_(Ca-L)峰值,被Dip 3μmol/L所抑制的I_(Ca-L)在冲洗5min后可得到部份恢复。但Dip对I_(Ca-L)的电压依赖特征,最大激活电压,以及I_(Ca-L)稳态激活无明显影响。在Dip3μmol/L存在下,半数激活电压(V_(0.5))和斜率参数(к)与对照组相比,差异均无显著性。V_(0.5)分别为(-12.8±1.7)mV和(-13.2±2.4)mV,к分别为(7.1±0.4)mV和(7.5±0.5)mV(P>0.05)。Dip3μmol/L可明显使钙电流稳态失活曲线左移,加速钙通道电压依赖性稳态失活。V_(0.5)分别为(-19.7±2.4)mV和(-31±6)mV,к分别为(3.6±0.3)mV和(1.8±0.2)mV(P<0.05).Dip 3μmol/L还使I_(Ca-L)从失活状态下的恢复明显减慢。结论:Dip主要作用于L-型钙通道的失活状态,加速钙通道失活,并使其从失活状态下恢复减慢,从而抑制I_(Ca-L)。