發(fā)布時(shí)間：2018-06-17 00:44

  本文選題：雌二醇 + 竇房結(jié)��； 參考：《河北醫(yī)科大學(xué)》2007年碩士論文

【摘要】： 流行病學(xué)調(diào)查顯示,心血管疾病的發(fā)病率和死亡率存在明顯的性別差異。絕經(jīng)前婦女心血管疾病的發(fā)病率明顯低于男性,而卵巢切除后或絕經(jīng)的婦女心血管疾病的發(fā)病率與死亡率明顯升高,與同齡男性相近或相同。雌激素是一類具有廣泛生物活性的甾體類激素。雌二醇(17-β-estradiol, Est)則是雌激素的一種主要的成分,它在體內(nèi)具有廣泛的生物學(xué)作用。雌激素的心血管保護(hù)效應(yīng)是多方面的,實(shí)驗(yàn)已證明雌激素有以下心血管保護(hù)作用:降低血管張力和血脂水平;抗氧化和保護(hù)冠脈血管內(nèi)皮;促進(jìn)血管內(nèi)皮細(xì)胞合成NO;抑制血小板粘附和聚集,抑制內(nèi)皮細(xì)胞的內(nèi)皮素及粘附因子的產(chǎn)生,進(jìn)一步抑制心肌損傷;阻止血管平滑肌細(xì)胞的鈣通道,抑制血管平滑肌細(xì)胞的增殖及遷移和細(xì)胞外基質(zhì)合成,從而抑制動(dòng)脈粥樣硬化形成,促使斑塊消退;抗凝血及促進(jìn)纖溶等作用。但近幾年的大規(guī)模的臨床試驗(yàn)卻未能證實(shí)雌激素替代療法(estrogen replacement therapy, HRT)對(duì)冠心病有防治的效力,相反,還能引起早期心血管事件的增加。我們以前的研究發(fā)現(xiàn),雌激素能夠抑制豚鼠乳頭肌的收縮,延長(zhǎng)動(dòng)作電位時(shí)程和有效不應(yīng)期;能夠抑制豚鼠心室肌細(xì)胞內(nèi)向整流鉀電流和延遲整流鉀電流,對(duì)抗實(shí)驗(yàn)性心律失常。目前,雌激素對(duì)竇房結(jié)自律細(xì)胞的作用還未見(jiàn)報(bào)道。本研究主要通過(guò) 細(xì)胞內(nèi)玻璃微電極技術(shù),研究雌激素對(duì)生理狀態(tài)下和模擬缺血狀態(tài)下對(duì)竇房結(jié)自律細(xì)胞的電生理活動(dòng)的影響,并探討其可能的作用機(jī)制。 1、雌二醇對(duì)生理狀態(tài)家兔竇房結(jié)自律細(xì)胞電活動(dòng)的影響 應(yīng)用細(xì)胞內(nèi)微電極技術(shù),觀察雌二醇對(duì)生理狀態(tài)家兔竇房結(jié)自律細(xì)胞電活動(dòng)的影響。結(jié)果如下: 1.1雌激素(1, 10, 100μmol/L)濃度依賴性延長(zhǎng)竇房結(jié)自律細(xì)胞動(dòng)作電位復(fù)極化50%(APD50)和90%時(shí)間(APD90),降低動(dòng)作電位幅值(APA),降低竇房結(jié)自律細(xì)胞放電頻率(RPF),減慢竇房結(jié)自律細(xì)胞動(dòng)作電位0期最大除極速率(Vmax)和舒張期自動(dòng)去極化速率(VDD),對(duì)竇房結(jié)自律細(xì)胞的最大舒張電位(MDP)無(wú)影響。在100μmol/L濃度下, APD50由對(duì)照的92.7±2.2 ms延長(zhǎng)至127.8±5.1 ms (P0.01), APD90由對(duì)照的124.3±5.0 ms延長(zhǎng)至153.4±12.8 ms (P0.01), Vmax和APA分別由對(duì)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分別由對(duì)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給予雌激素受體阻斷劑它莫昔芬(Tamoxifen, 10μmol/L),不能阻斷雌激素(10μmol/L)對(duì)竇房結(jié)自律細(xì)胞動(dòng)作電位的抑制效應(yīng)。 1.3給予一氧化氮合酶抑制劑L-NAME(100μmol/L)能完全阻斷雌激素(10μmol/L)對(duì)竇房結(jié)自律細(xì)胞動(dòng)作電位的抑制效應(yīng)。 以上結(jié)果表明,雌二醇(10μmol/L)對(duì)家兔竇房結(jié)自律細(xì)胞的電活動(dòng)具有明顯的抑制作用,此作用可能是通過(guò)非基因組機(jī)制而發(fā)揮。 2、雌二醇對(duì)模擬缺血狀態(tài)家兔竇房結(jié)自律細(xì)胞電活動(dòng)的影響 應(yīng)用細(xì)胞內(nèi)微電極技術(shù),觀察雌二醇對(duì)模擬缺血狀態(tài)家兔竇房結(jié)自律細(xì)胞電活動(dòng)的影響。結(jié)果如下: 2.1模擬缺血狀態(tài)下,竇房結(jié)自律細(xì)胞動(dòng)作電位APD50和APD90分別為70.6±6.8 ms和104.8±9.3 ms,較對(duì)照組的90.4±4.9 ms和127.6±7.9 ms明顯縮短(P0.01); RPF為113.6±10.5 beat/min,較對(duì)照組的159.8±6.9 beat/min明顯降低(P0.01); VDD為25.5±5.5 mv/s,較對(duì)照組的57.7±5.9 mv/s明顯降低(P0.01). 2.2雌二醇(10μmol/L)能夠部分對(duì)抗模擬缺血狀態(tài)下動(dòng)作電位各參數(shù)的變化。 2.3它莫昔芬(Tamoxifen, 10μmol/L)預(yù)處理不能阻斷模擬缺血狀態(tài)下雌二醇的作用。 以上結(jié)果表明,雌二醇(10μmol/L)能夠?qū)�抗模擬缺血引起的竇房結(jié)自律細(xì)胞電生理學(xué)參數(shù)的變化,具有心臟保護(hù)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.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2007
【分類號(hào)】：R33

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