雌二醇对家兔窦房结自律细胞电活动的影响

发布时间：2018-06-17 00:44

本文选题：雌二醇 + 窦房结　；参考：《河北医科大学》2007年硕士论文

【摘要】： 流行病学调查显示,心血管疾病的发病率和死亡率存在明显的性别差异。绝经前妇女心血管疾病的发病率明显低于男性,而卵巢切除后或绝经的妇女心血管疾病的发病率与死亡率明显升高,与同龄男性相近或相同。雌激素是一类具有广泛生物活性的甾体类激素。雌二醇(17-β-estradiol, Est)则是雌激素的一种主要的成分,它在体内具有广泛的生物学作用。雌激素的心血管保护效应是多方面的,实验已证明雌激素有以下心血管保护作用:降低血管张力和血脂水平;抗氧化和保护冠脉血管内皮;促进血管内皮细胞合成NO;抑制血小板粘附和聚集,抑制内皮细胞的内皮素及粘附因子的产生,进一步抑制心肌损伤;阻止血管平滑肌细胞的钙通道,抑制血管平滑肌细胞的增殖及迁移和细胞外基质合成,从而抑制动脉粥样硬化形成,促使斑块消退;抗凝血及促进纤溶等作用。但近几年的大规模的临床试验却未能证实雌激素替代疗法(estrogen replacement therapy, HRT)对冠心病有防治的效力,相反,还能引起早期心血管事件的增加。我们以前的研究发现,雌激素能够抑制豚鼠乳头肌的收缩,延长动作电位时程和有效不应期;能够抑制豚鼠心室肌细胞内向整流钾电流和延迟整流钾电流,对抗实验性心律失常。目前,雌激素对窦房结自律细胞的作用还未见报道。本研究主要通过细胞内玻璃微电极技术,研究雌激素对生理状态下和模拟缺血状态下对窦房结自律细胞的电生理活动的影响,并探讨其可能的作用机制。 1、雌二醇对生理状态家兔窦房结自律细胞电活动的影响应用细胞内微电极技术,观察雌二醇对生理状态家兔窦房结自律细胞电活动的影响。结果如下: 1.1雌激素(1, 10, 100μmol/L)浓度依赖性延长窦房结自律细胞动作电位复极化50%(APD50)和90%时间(APD90),降低动作电位幅值(APA),降低窦房结自律细胞放电频率(RPF),减慢窦房结自律细胞动作电位0期最大除极速率(Vmax)和舒张期自动去极化速率(VDD),对窦房结自律细胞的最大舒张电位(MDP)无影响。在100μmol/L浓度下, APD50由对照的92.7±2.2 ms延长至127.8±5.1 ms (P0.01), APD90由对照的124.3±5.0 ms延长至153.4±12.8 ms (P0.01), Vmax和APA分别由对照的4.8±0.4 v/s和68.7±6.8 mv降低到3.0±0.8 v/s (P0.01),和60.3±6.5 mv (P0.05), RPF和VDD分别由对照的169.9±13.6 beat/min和61.3±9.2 mv/s下降到136.8±23.6 beat/min和33.6±12.2 mv/s (P0.01). 1.2给予雌激素受体阻断剂它莫昔芬(Tamoxifen, 10μmol/L),不能阻断雌激素(10μmol/L)对窦房结自律细胞动作电位的抑制效应。 1.3给予一氧化氮合酶抑制剂L-NAME(100μmol/L)能完全阻断雌激素(10μmol/L)对窦房结自律细胞动作电位的抑制效应。以上结果表明,雌二醇(10μmol/L)对家兔窦房结自律细胞的电活动具有明显的抑制作用,此作用可能是通过非基因组机制而发挥。 2、雌二醇对模拟缺血状态家兔窦房结自律细胞电活动的影响应用细胞内微电极技术,观察雌二醇对模拟缺血状态家兔窦房结自律细胞电活动的影响。结果如下: 2.1模拟缺血状态下,窦房结自律细胞动作电位APD50和APD90分别为70.6±6.8 ms和104.8±9.3 ms,较对照组的90.4±4.9 ms和127.6±7.9 ms明显缩短(P0.01); RPF为113.6±10.5 beat/min,较对照组的159.8±6.9 beat/min明显降低(P0.01); VDD为25.5±5.5 mv/s,较对照组的57.7±5.9 mv/s明显降低(P0.01). 2.2雌二醇(10μmol/L)能够部分对抗模拟缺血状态下动作电位各参数的变化。 2.3它莫昔芬(Tamoxifen, 10μmol/L)预处理不能阻断模拟缺血状态下雌二醇的作用。以上结果表明,雌二醇(10μmol/L)能够对抗模拟缺血引起的窦房结自律细胞电生理学参数的变化,具有心脏保护作用。
[Abstract]:The incidence and mortality of cardiovascular diseases were significantly different. The incidence of cardiovascular disease in premenopausal women was significantly lower than that in men. The incidence and mortality of cardiovascular diseases in women after ovariectomy or menopause were significantly higher than those of men of the same age. 17- beta -estradiol (Est), a major component of estrogen, is a major component of estrogen. It has extensive biological effects in the body. The cardiovascular protective effects of estrogen are multifaceted. Experiments have shown that estrogen has the following protective effects on cardiovascular disease: lowering blood vessel tension and blood lipid levels; antioxidation and To protect vascular endothelial cells, promote vascular endothelial cells to synthesize NO, inhibit adhesion and aggregation of platelets, inhibit the production of endothelin and adhesion factors of endothelial cells, further inhibit myocardial injury, prevent the calcium channel of vascular smooth muscle cells, inhibit the proliferation and migration of vascular smooth muscle cells and synthesis of extracellular matrix, and inhibit the braking of vascular smooth muscle cells. The formation of atherosclerotic veins causes plaque to decline, anticoagulant and fibrinolysis. But in recent years, large scale clinical trials have failed to confirm the effectiveness of estrogen replacement therapy (estrogen replacement therapy, HRT) on coronary heart disease. On the contrary, it can also cause an increase in early cardiovascular events. Our previous study found that the female was female. Hormone can inhibit the contraction of guinea pig papillary muscles, prolong action potential time and effective refractory period. It can inhibit the internal rectifying potassium current and delayed rectifier potassium current of guinea pig ventricular myocytes and antagonism experimental arrhythmia. At present, the role of estrogen on sinus node self-discipline cells has not yet been reported. This study mainly through the study.
The effect of estrogen on the electrophysiological activities of the self-regulated sinoatrial node in the physiological and simulated ischemic states and its possible mechanism were investigated by the intracellular glass microelectrode technique.
1, the effect of estradiol on the electrical activity of sinoatrial node autonomic cells in physiological rabbits
The effects of estradiol on the electrical activity of sinoatrial node autonomic cells in rabbits were observed by intracellular microelectrode technique.
1.1 estrogen (1, 10, 100 mol/L) had a concentration dependent prolonged action potential repolarization 50% (APD50) and 90% time (APD90), decreased the amplitude of action potential (APA), reduced the frequency of autonomic cell discharge (RPF) in sinoatrial node (RPF), and slowed down the maximum depolarization rate (Vmax) and diastolic depolarization rate of the autonomic fine cell action potential (Vmax) and diastolic phase of the sinoatrial node. (VDD) did not affect the maximum diastolic potential (MDP) of the sinoatrial node autonomic cells. Under the concentration of 100 mol/L, APD50 was extended from 92.7 + 2.2 ms of the control to 127.8 + 5.1 MS (P0.01), and APD90 from 124.3 + 5 ms to 153.4 + 12.8 MS (P0.01). And 60.3 + 6.5 MV (P0.05), RPF and VDD decreased from 169.9 + 13.6 beat/min and 61.3 + 9.2 mv/s to 136.8 + 23.6 beat/min and 33.6 12.2 mv/s (P0.01), respectively.
1.2 the estrogen receptor blocker, Mo Xifen (Tamoxifen, 10 mu mol/L), did not block the inhibitory effect of estrogen (10 u mol/L) on the action potential of the sinoatrial node autonomic cell.
1.3 nitric oxide synthase inhibitor L-NAME (100 mol/L) can completely block the inhibitory effect of estrogen (10 mol/L) on the action potential of sinoatrial node autonomic cells.
The above results show that the estradiol (10 mol/L) can inhibit the electrical activity of the autonomic cells of the sinoatrial node in rabbits. This effect may be played through the non genomic mechanism.
2, the effect of estradiol on the electrical activity of sinoatrial node autonomic cells in rabbits with simulated ischemia.
The effects of estradiol on the electrical activity of sinoatrial node autonomic cells in rabbits with simulated ischemia were observed by intracellular microelectrode technique.
2.1 in simulated ischemic state, the action potential APD50 and APD90 of the sinoatrial node were 70.6 + 6.8 ms and 104.8 + 9.3 MS, respectively, compared with 90.4 + 4.9 MS and 127.6 + 7.9 MS in the control group (P0.01), RPF was 113.6 + 10.5 beat/min, compared with 159.8 + 6.9 beat/min in the control group (P0.01). 9 mv/s was significantly decreased (P0.01).
2.2 estradiol (10 mu mol/L) can partially antagonized the changes of action potential under simulated ischemia.
2.3 its pretreatment with Mo Xifen (Tamoxifen, 10 mol/L) can not block the effect of estradiol under simulated ischemia.
The above results indicate that estradiol (10 mu mol/L) can counteract the changes of electrophysiological parameters induced by simulated ischemia in autonomic cells of sinoatrial node, and has cardioprotective effect.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R33

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