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1.
目的探讨糖尿病大鼠心肌病变是否与钠钙交换蛋白Ⅰ亚型(NCX1)及肌浆网钙泵2a亚型(SERCA2a)表达水平变化有关。方法大鼠腹腔注射链佐霉素制备实验性糖尿病大鼠模型。将大鼠成模后分别于4w、6w和8w时取心肌组织,进行病理学检查及计算心脏相对重量观察心肌病变程度;应用RT-PCR方法扩增NCX1和SERCA2a两种产物,计算NCX1与SERCA2amRNA相对数量的变化,并与相应周数的正常对照组进行比较。结果糖尿病各组心脏湿重与体重的比值均明显高于对照组,病理检查显示心肌细胞呈不同程度变性坏死;4w,6w糖尿病组NCX1和SERCA2amRNA的量有所降低,但无统计学差别,而8w时,糖尿病组NCX1和SERCA2amRNA相对含量比对照组明显减少(P<0.05)。结论在糖尿病合并心肌病变时,大鼠心肌的NCX1与SERCA2a的mRNA水平降低,提示其心脏功能的减退与NCX1和SER-CA2a的mRNA水平降低有一定关系。  相似文献   

2.
目的检测毒毛旋花子苷原(Str)对正常和心衰心肌单细胞收缩力和钙瞬变的作用。方法采用降主动脉缩窄建立豚鼠慢性充血性心力衰竭模型,酶解法急性分离左室心肌细胞,同步检测Str对单个正常细胞(NC)和心衰细胞(FC)收缩力和钙瞬变的影响,并检测Str是否具有钙增敏作用。结果0.1、1、10、25μmol.L-1Str可使NC和FC收缩幅度、钙瞬变幅度呈剂量依赖性增大;同剂量时,Str对FC的作用比NC更明显;但Str对NC和FC收缩时程及钙瞬变时程均无影响。Str对NC具有钙增敏作用,而对FC没有。结论Str增加FC的收缩力和钙瞬变作用比NC更明显,而Str仅对NC具有钙增敏作用。  相似文献   

3.
应用全细胞电压钳技术的斜坡脉冲程序 ,测定离体豚鼠心肌细胞准稳态电流 -电压关系曲线 ,研究E- 40 31增强 Na /Ca2 交换电流的机理 .结果表明蛋白激酶 C激动剂十四酰佛波乙酯 ( TPA) 5,1 0和1 5nmol· L-1使膜电位 50 m V时的 Ni2 敏感电流分别增加 ( 1 1 6± 43) % ,( 2 2 5± 63) %和 ( 2 89±69) % .使膜电位 - 1 0 0 m V时的 Ni2 敏感电流分别增加 ( 2 9± 1 7) % ,( 1 0 4± 2 1 ) %和 ( 1 40± 2 9) % .蛋白激酶 C拮抗剂他莫昔芬 2 0 μmol· L-1可完全阻断 E- 40 31和 TPA对该电流的刺激作用 .结果提示 ,E- 40 31通过蛋白激酶 C途径激动 Na /Ca2 交换 .  相似文献   

4.
目的 研究苯丙 -甲硫 -精 -苯丙氨酸 (FMRFa)多肽对心肌细胞膜钙瞬变触发的 Na+ / Ca2 + 交换尾电流的影响。方法 采用蛋白酶 E急性分离的豚鼠心室肌细胞。利用全细胞膜片钳技术观察 FMRFa多肽对心肌细胞膜 Na+ / Ca2 + 交换尾电流的作用。结果  FMRFa多肽 1、5、10、2 0μm可分别抑制 Na+ / Ca2 + 交换尾电流(13± 3) % ,(2 5± 7) % ,(73± 9) %和 (110± 10 ) %。结论  FMRFa多肽可剂量依赖性地抑制豚鼠心室肌细胞膜钙瞬变触发的 Na+ / Ca2 +交换尾电流  相似文献   

5.
AIM: To study the effects of E-4031 on the Na+/Ca2+ exchange currents (INa/Ca). METHODS: The quasi-steady state current-voltage relationship from the isolated rat ventricular myocytes was measured using whole-cell voltage-clamp techniques with a ramp pulse protocol. RESULTS: At potential of mV, E-4031 5, 10, and 20 mumol.L-1 increased Ni(2+)-sensitive current from (0.48 +/- 0.12), to (0.78 +/- 0.20), (0.96 +/- 0.16), and (1.15 +/- 0.13) pA/pF, respectively; tetradecanoylphorbol acetate (TPA) 50 nmol.L-1 increased Ni(2+)-sensitive current from (0.60 +/- 0.16) to (1.33 +/- 0.25) pA/pF. Tamoxifen 20 mumol.L-1 completely prevented the current changes induced by E-4031 and TPA. CONCLUSION: E-4031 stimulates the Na+/Ca2+ exchange via a protein kinase C-dependent pathway.  相似文献   

6.
应用全细胞电压钳技术的斜坡脉冲程序,测定离体豚鼠心肌细胞准稳态电流-电压关系曲线,研究E-4031增强Na+/Ca2+交换电流的机理. 结果表明蛋白激酶C激动剂十四酰佛波乙酯(TPA)5,10和15 nmol·L-1使膜电位+50 mV时的Ni2+敏感电流分别增加(116±43)%,(225±63)% 和(289±69)%. 使膜电位-100 mV时的Ni2+敏感电流分别增加(29±17)%,(104±21)%和(140±29)%. 蛋白激酶C拮抗剂他莫昔芬20 μmol·L-1可完全阻断E- 4031和TPA对该电流的刺激作用. 结果提示,E-4031通过蛋白激酶C途径激动Na+/Ca2+交换.  相似文献   

7.
应用全细胞电压钳的斜坡脉冲程序测定离体豚鼠心肌细胞准稳态电流电压关系曲线,研究Ⅲ类抗心律失常药E-4031对Na+/Ca2+交换电流的影响,结果表明E-40310.1,1.0,10,50μmol·L-1使Ni2+敏感电流浓度依赖性增加,膜电位+50mV时分别增加(70±38)%,(91±53)%,(118±63)%,(122±51)%;膜电位-100mV时增加(25±20)%,(51±32)%,(113±84)%,(93±73)%。提示E-4031对心室肌细胞Na+/Ca2+交换电流的增强作用可能是其正性变力作用的重要机理。  相似文献   

8.
Ca~(2+)平衡是维持心肌细胞正常电生理活动的重要前提。在各种机制中,肌质网Ca-ATPase与肌膜Na/Ca交换蛋白对于维持胞内Ca~(2+)的平衡发挥主要作用。其中肌膜Na/Ca交换蛋白是Ca~(2+)排出胞外的主要途径,并通过调节细胞内静息状态下[Ca~(2+)]调节肌质网的[Ca(2+)]含量,从而调节心肌细胞的收缩力。少量Ca(2+)内流入胞后可触发肌质网释放大量Ca(2+)(CICR)。已证实动作电位峰电位及平台期有Ca(2+)通过Na/Ca内流,这种除极化诱导的Ca(2+)经Na/Ca内流可能是触发CICR的主要因素。总之Na/Ca交换蛋白在兴奋-收缩耦联中的作用需要重新加以评价。  相似文献   

9.
目的:观察复合离子盐对老年人细胞内Na^+、K^+、Ca^2+及红细胞膜钠泵和钙泵活性的影响。方法:在天津市河东区社区中抽取226例老年人作为研究对象.其中高血压者112例。正常血压者114例。两者再随机分为离子盐组和普通加碘盐组.分别给予复合离子盐和普通加碘盐摄入,6个月后观察研究对象细胞内Na^+、K^+、Ca^2+及钠泵、钙泵活性的变化。结果:6个月时高血压患者中离子盐组细胞内钠、钙离子浓度低于基线水平(P〈0.05),但钾离子无明显变化。离子盐组钠泵、钙泵活性均明显高于基线水平(P〈0.05),但在正常血压者中,2组与基线水平比较差异无统计学意义。结论:复合离子盐可增强钠泵、钙泵活性,使细胞内的钠、钙含量减少。  相似文献   

10.
The protective effects of the Na+/H+ exchange inhibitors amiloride, EIPA (5‐(N‐ethyl‐N‐isopropyl)‐amiloride), and HOE 694 (3‐methylsulfonyl‐4‐(1‐piperidino) benzoyl‐guanidine) and the Na+/Ca2+ exchange inhibitor, DCB (3,4‐Dichlorobenzamil) on ischemia (30 min) / reperfusion (30 min) injury were studied using Langendorff perfused rat hearts. EIPA and HOE 694 given before ischemia protected the heart during reperfusion from mechanical and metabolic disturbances. A weak protective effect was observed with amiloride, but not with DCB. The cardioprotective efficacies of these compounds correlated with their potencies as Na+/H+ exchange inhibitors as assessed by the NH4Cl prepulse method. None of the inhibitors was effective when given at reperfusion. EIPA and HOE 694 decreased myocardial rigidity as assessed by the resting tension (RT) which elevated during reperfusion. EIPA led to a more marked attenuation of RT elevation during reperfusion rather than ischemia, whereas diltiazem, a Ca2+ channel blocker, suppressed RT elevation during ischemia but did not cause a further attenuation of RT during reperfusion. Treatment with EIPA as well as diltiazem before ischemia showed a direct negative chronotropic effect. Cardioprotective effects were also observed with diltiazem. These results suggest that Na+/H+ exchange plays a more important role in ischemia‐reperfusion‐induced myocardial injury than does Na+/Ca2+ exchange. The cardioprotective effects of EIPA appear to be produced by Ca2+ channel blockade during ischemia and by Na+/H+ exchange inhibition during reperfusion. Drug Dev. Res. 48:160–170, 1999. © 1999 Wiley‐Liss, Inc.  相似文献   

11.
1. Pyruvate has been shown to enhance the contractile performance of cardiac muscle when provided as an alternative substrate to glucose. The aims of the present study were to determine whether the inotropic effects of pyruvate are due to increased mobilization of intracellular Ca2+ ([Ca2+]i) and to compare the effects of pyruvate on [Ca2+]i levels in myocytes from normal and diabetic animals. 2. Fura-2 was used to monitor [Ca2+]i in ventricular myocytes isolated from control and streptozotocin-treated male Wistar rats. The experiments were performed at 25 degrees C, with an extracellular [Ca2+] of 1.5 mmol/L and either 10 mmol/L glucose or 10 mmol/L pyruvate as the substrate. 3. In myocytes from both control and diabetic rats, increasing the stimulus frequency from 0.33 to 2.0 Hz resulted in significant increases in resting and peak [Ca2+]i as well as in the amplitude of the [Ca2+]i transient, irrespective of substrate. Compared with glucose, pyruvate significantly increased resting and peak [Ca2+]i and the amplitude of the [Ca2+]i transient at each stimulus frequency in myocytes from both control and diabetic animals. However, the extent of potentiation of the [Ca2+]i transient amplitude produced by pyruvate was significantly less in myocytes from the diabetic rats. 4. The rate of restitution of the [Ca2+]i transient was used as an index of the rate of Ca2+ cycling by the sarcoplasmic reticulum (SR). Pyruvate enhanced the rate of restitution in control but not diabetic rat cells. 5. The time course of decay of the [Ca2+]i transient was analysed as a measure of the rate of removal of Ca2+ from the cytosol. Pyruvate tended to increase the rate of decay in cells from control but not diabetic animals. The rate of decay was slower in cells from diabetic animals compared with controls. 6. The data reveal that pyruvate increases SR Ca2+ cycling, leading to greater Ca2+ release and an increase in the amplitude of the [Ca2+]i transient. Therefore, it seems highly likely that increased [Ca2+]i mobilization is responsible for the previously reported positive inotropic actions of pyruvate. These effects of pyruvate are attenuated in diabetic rat cells, which may reflect an impaired capacity of mitochondria in diabetic hearts to oxidize pyruvate, thus limiting potential energetic benefits.  相似文献   

12.
1. The effects of endothelin-1 (ET-1) on intracellular Ca2+ ion level and cell contraction were simultaneously investigated in rabbit ventricular cardiac myocytes loaded with indo-1/A1. The role of Na+/Ca2+ exchange in ET-1-induced positive inotropic effect (PIE) was examined by using KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulphonate), a selective inhibitor of reverse mode Na+/Ca2+ exchange. 2. ET-1 at 0.3 pM - 1 nM increased cell contraction and Ca2+ transient (CaT) with EC50 values of 2.9 pM and 1.2 pM, respectively, and the increase in amplitude of CaT was much smaller relative to the PIE: ET-1 at 1 nM increased peak cell shortening by 237%, while it increased peak CaT by 167%. For a given level of PIE, ET-1-induced increase in CaT was much smaller than that induced by elevation of [Ca2+]o and by isoprenaline. Therefore, ET-1 shifted the relationship between peak CaT and cell shortening to the left relative to the relationship for increase in [Ca2+]o, an indication that ET-1 increased myofibrillar Ca2+ sensitivity. 3. KB-R7943 at 0.1 microM and higher inhibited contraction and CaT induced by 0.1 nM ET-1 and at 0.3 microM it abolished the increase in CaT while inhibiting the PIE by 48.1%. Over concentration range of 0.1-0.3 microM, KB-R7943 neither inhibited baseline contraction and CaT nor the isoprenaline-induced response, although at 1 microM and higher it had a significant inhibitory action on these responses. 4. These results indicate that in rabbit ventricular myocytes both increases in CaT and myofibrillar Ca2+ sensitivity contribute to the ET-induced PIE, and the activation of reverse mode Na+/Ca2+ exchange may play a crucial role in increase in CaT induced by ET-1 in rabbit ventricular cardiac myocytes.  相似文献   

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