本文選題：間歇性低壓低氧　切入點：異丙腎上腺素　出處：《河北醫(yī)科大學》2007年碩士論文

【摘要】： 目的:近年來,大量研究表明間歇性低壓低氧(intermittent hypobaric hypoxia, IHH)處理具有明顯的心臟保護作用,并越來越受到人們的重視和關注,已成為臨床醫(yī)學、高原醫(yī)學和運動醫(yī)學研究的熱點之一。眾多研究顯示,IHH處理顯著提高心肌抗缺血/再灌注、缺氧/復氧損傷的能力,表現(xiàn)為顯著減輕缺血再灌注后心臟舒縮功能降低,縮小冠脈閉塞所致心肌梗死面積,以及抗缺血再灌注心律失常作用。目前已知IHH心臟保護作用主要涉及以下幾方面,如IHH可以改善心肌物質(zhì)與能量代謝的能力,增加氧的有效利用、減少ATP耗竭,增加心肌毛細血管密度、改善心肌供血,增強心肌抗氧化酶活性,增加心肌對氧自由基的抵抗力;開放KATP通道,尤其是線粒體上的KATP通道;減弱缺血/再灌注時肌漿網(wǎng)的損傷,維持Na+/Ca2+交換體(NCX)的活性,減少鈣超載;抑制線粒體通透轉(zhuǎn)換孔的開放;上調(diào)心肌iNOS的mRNA和蛋白的水平,導致NO的生成增多;抑制心肌細胞的凋亡等等。但有關IHH心臟保護作用的確切機制遠未闡明。心臟β腎上腺素能受體在正常心臟活動調(diào)節(jié)中發(fā)揮重要作用,其功能下調(diào)或受體阻斷可表現(xiàn)某種心臟保護作用。有報道IHH可減輕心肌缺血期鈣超載程度,其機理可能與α1B腎上腺素能受體亞型有關。IHH對心臟β腎上腺素能受體影響如何,或心臟β腎上腺素能受體是否參與IHH心臟保 護作用未見報道。本研究應用經(jīng)典的細胞內(nèi)微電極記錄技術及肌肉收縮描記方法,觀察β腎上腺素能受體激動劑-異丙腎上腺素(ISO)對IHH處理14天、28天和42天大鼠右心室乳頭肌動作電位和機械收縮的影響,以探討IHH對大鼠心肌β腎上腺素能受體的影響。 方法:雄性Sprague-Dawley(SD)大鼠,以戊巴比妥鈉(30-35mg/kg,i.p.)腹腔注射麻醉,仰位固定,開胸迅速取出心臟,置于冷凍(0-4℃)改良臺氏液中以制備右室乳頭肌標本。制備好的乳頭肌腱膜端固定于張力換能器,另一端用不銹鋼針固定于灌流槽的硅橡膠上。用改良臺氏液(pH 7.4±0.05)以12ml/min的速度灌流標本,溫度維持在37℃,并持續(xù)充以純氧。標本在灌流液中平衡一小時后開始實驗。以刺激頻率為1HZ,波寬3ms,強度為2倍閾強度的矩形脈沖刺激標本,誘發(fā)乳頭肌動作電位和收縮。用尖端電阻10-20兆歐的玻璃微電極緩慢插入乳頭肌細胞內(nèi),記錄細胞內(nèi)動作電位。電活動經(jīng)微電極放大器、高速數(shù)模轉(zhuǎn)換器儲存于計算機,通過我室自編的程序進行自動采集、分析。動作電位參數(shù)包括靜息電位(RP)、動作電位(OS)、動作電位幅值(APA)、動作電位0相最大上升速率(V_(max))、復極化50%(APD_(50))和90%的時間(APD_(90))。機械收縮通過壓力換能器儲存于計算機,肌肉收縮參數(shù)包括最大收縮張力(P_(max))和最大張力上升速度(P_(dT/dt))。用累加給藥法觀察不同濃度異丙腎上腺素(ISO, 10~(-8) ,10~(-7),10~(-6)mol/L)對大鼠右心室乳頭肌動作電位和機械收縮的影響。 結(jié)果:(1)IHH明顯延長大鼠右心室乳頭肌動作電位時程:APD_(50)由對照組的23.2±5.5 ms分別延長為35.0±7.6 ms、31.7±6.0 ms、48.3±3.4 ms;APD90由對照組的72.5±9.8 ms分別延長為100.2±5.9 ms、99.2±9.0 ms、133.8±21.2 ms;(2)ISO濃度依賴性地增加各組動物右心室乳頭肌動作電位幅值(APA)、動作電位超射(OS)、動作電位0期最大上升速率(V_(max)),延長動作電位復極化50%(APD_(50))、復極化90%(APD90)時間,并增加機械收縮的最大收縮張力(P_(max))和最大張力上升速度(P_(dT/dt));(3)與對照組相比較,IHH組ISO引起的乳頭肌動作電位及機械收縮的反應明顯降低。 結(jié)論:IHH明顯降低大鼠右心室乳頭肌對ISO的反應,表明心臟β腎上腺素能受體功能下降,此作用可能是IHH心臟保護作用的機制之一。
[Abstract]:Objective: in recent years, a large number of studies show that intermittent hypobaric hypoxia (intermittent hypobaric, hypoxia, IHH) treatment has protective effect on the heart obviously, and people pay more and more attention and concern, has become one of the hot points of clinical medicine, plateau medicine and sports medicine. Many studies showed that IHH treatment significantly improved myocardial ischemia / reperfusion, hypoxia / reoxygenation injury, showed significantly reduced after ischemia reperfusion of cardiac systolic and diastolic function decreased, reducing the area of myocardial infarction caused by coronary artery occlusion, ischemia reperfusion and anti arrhythmia effect. The cardioprotective effects of known IHH mainly involves the following aspects, such as the ability of IHH can improve myocardial energy and matter the metabolism, increase the effective utilization of oxygen, reduce ATP depletion, increase myocardial capillary density, improve myocardial ischemia, enhance myocardial antioxidant enzyme activity, increased myocardial oxygen Radical resistance; open KATP channel, especially on the mitochondrial KATP channel; weaken the damage of sarcoplasmic reticulum during ischemia / reperfusion, maintain the Na+/Ca2+ exchange (NCX) activity, reduce calcium overload; inhibition of mitochondrial permeability transition pore opening; mRNA and upregulation of myocardial iNOS level increase the formation of NO; inhibition of myocardial apoptosis and so on. But the exact mechanism of the cardioprotective effects of IHH are far from clear. Cardiac beta adrenergic receptors play an important role in the regulation of normal cardiac activity, its function can be reduced or blocking the heart protective effect is a table. It has been reported that IHH can reduce the degree of myocardial ischemia during calcium overload 1B, its mechanism may be related to alpha adrenergic receptor subtype.IHH on cardiac beta adrenergic receptor to, or cardiac beta adrenergic receptors are involved in IHH cardiac protection
Protective effect has not been reported. This study used the classic intracellular microelectrode recording technique and muscle contraction were recorded, the observation of beta adrenergic receptor agonist isoproterenol (ISO) of IHH for 14 days, 28 days and 42 days of rat right ventricular papillary muscle action potential and mechanical contraction effect can influence on myocardial beta adrenergic receptor in rats to investigate the IHH.
Methods: male Sprague-Dawley rats (SD) with sodium pentobarbital (30-35mg/kg, i.p.) intraperitoneal injection of anesthesia, fixed on back and chest quickly remove the heart, placed in the freezer (0-4 DEG C) modified Tyrode's solution in preparation of right ventricular papillary muscle specimens. The nipple tendon membrane prepared end is fixed on the tension the transducer, the other end with a stainless steel needle is fixed in the perfusion chamber. The silicone rubber with modified Tyrode's solution (pH 7.4 + 0.05) at a speed of 12ml/min perfusion was maintained at a temperature of 37 DEG C, and continuously filled with pure oxygen. The specimen began to experiment in the perfusate after one hour. In order to balance the stimulus frequency 1HZ, 3MS wave width, intensity is 2 times the threshold intensity of rectangular pulse stimulation specimens, action potential of papillary muscle and contraction induced by glass microelectrode. The tip resistance of 10-20 megohms slowly inserted into the papillary muscle cell, intracellular recording action potentials. The electrical activity of the microelectrode amplifier, High Speed DAC storage Stored in the computer room, through my own program for automatic acquisition and analysis. The action potential parameters including resting potential (RP), action potential (OS), amplitude of action potential (APA), phase 0 of the action potential maximum rise rate (V_ (max) 50% (APD_), repolarization (50) and 90%) time (APD_ (90)). The mechanical contraction pressure transducer is stored in the computer, the muscle contraction parameters including maximum isometric tension (P_ (max)) and the maximum tension of rising velocity (P_ (dT/dt)). The effects of different concentrations of isoproterenol with the cumulative dosing method (ISO, 10~ (-8), 10~ (-7), 10~ (-6) mol/L) effect on rat right ventricular papillary muscle action potential and contraction.
Results: (1) IHH significantly prolonged rat right ventricular papillary muscle action potential duration: APD_ (50) by 23.2 in the control group were extended to 35 + 5.5 MS + 7.6 MS, 31.7 MS + 6, 48.3 + 3.4 MS; APD90 from a control group of 72.5 + 9.8 MS were extended to 100.2 + 5.9 MS, 99.2 + 9 ms 133.8 + 21.2 MS; (2) ISO concentration dependently increased in each animal right ventricular papillary muscle action potential amplitude (APA), action potential overshoot (OS), action potential 0 maximum rise rate (V_ (max)), prolonged action potential repolarization (APD_ 50% (50)), 90% (APD90) repolarization time and increase the maximum isometric tension mechanical contraction (P_ (max)) and the maximum tension of rising velocity (P_ (dT/dt)); (3) compared with the control group, the action potential of papillary muscle and mechanical contraction caused by ISO of the IHH group was significantly decreased.
Conclusion: IHH significantly decreases the response of the right ventricular papillary muscles to ISO, indicating that the function of cardiac beta adrenergic receptor is decreased, which may be one of the mechanisms of IHH cardioprotection.

【學位授予單位】：河北醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2007
【分類號】：R363

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相關期刊論文 前1條

1 鐘寧,張翼,方奇志,周兆年;間歇性低氧誘導的心肌熱休克蛋白70表達增加大鼠心臟對缺血損傷的耐受(英文)[J];Acta Pharmacologica Sinica;2000年05期

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本文編號：1693038