本文選題：全細(xì)胞膜片鉗 + 鈉-鈣交換體�。� 參考：《山西醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:建立哇巴因誘發(fā)正常和心力衰竭大鼠心律失常模型,觀察抗鈉-鈣交換體NCX-2D2抗體對(duì)模型大鼠心律失常的影響,并分析其可能的作用機(jī)制。方法:1.哇巴因誘發(fā)成年大鼠離體和在體心臟心律失常模型的建立(1)哇巴因誘發(fā)大鼠離體心律失常模型健康SD大鼠,50 mg·kg~(-1)戊巴比妥鈉腹腔注射麻醉后,開胸游離心臟并且懸掛于Langendorff裝置上,進(jìn)行主動(dòng)脈逆行灌流,流速為8mL·min-1,觀察至少30 min待心電圖波形穩(wěn)定后使用給藥泵給藥,記錄心電圖。實(shí)驗(yàn)分組如下:①正常對(duì)照組:含2.5 mmol·L-1 CaCl2的臺(tái)氏液灌流;② 2D2+CaCl2 組:含 10 μg·ml~(-1) NCX-2D2 抗體和 2.5 mmol·L-1 CaCl2 的臺(tái)氏液灌流;③ Oua+CaCl2組:含5μmol·L-1 Ouabain 和 2.5 mmol·L-1 CaCl2 的臺(tái)氏液灌流;④ 2D2+Oua+CaCl2 組:含 10 μg ml~(-1) NCX-2D2 抗體、5 μmol·L-1 Ouabain 和 2.5 mmol.L-1 CaCl2的臺(tái)氏液灌流。心電圖記錄藥物干預(yù)后30 min內(nèi)室性期前收縮個(gè)數(shù),室速和室顫發(fā)生率及持續(xù)時(shí)間。(2)哇巴因誘發(fā)麻醉大鼠心律失常模型健康SD大鼠用30 mg·kg~(-1) 水合氯醛腹腔注射麻醉后將大鼠置于鼠板上,連接固定肢體導(dǎo)聯(lián)。采用BL-420F生物機(jī)能實(shí)驗(yàn)系統(tǒng)記錄大鼠Ⅱ?qū)?lián)心電圖,連續(xù)觀察30min心電圖無(wú)異常后尾靜脈給藥,記錄藥物干預(yù)后1 h內(nèi)室性期前收縮的個(gè)數(shù)、室速和室顫持續(xù)時(shí)間及發(fā)生率。2.大鼠心力衰竭模型的制備取成年健康SD大鼠,隨機(jī)分為偽手術(shù)組和心衰組,術(shù)前禁飲禁食24 h,稱量大鼠體重,給予水合氯醛(30 mg·kg~(-1))腹腔注射麻醉。待大鼠麻醉后固定于鼠板上,脫去大鼠腹部的毛,于大鼠左脊肋角后縱向切口 2 cm,鈍性分離暴露腹主動(dòng)脈,以7號(hào)針針頭與腹主動(dòng)脈一起結(jié)扎,然后抽出針頭形成腹主動(dòng)脈狹窄,關(guān)閉腹腔。偽手術(shù)組僅不結(jié)扎腹主動(dòng)脈,其余操作均與心衰組相同。術(shù)后3天每天腹腔注射青霉素20萬(wàn)單位預(yù)防感染。3.超聲心動(dòng)圖檢測(cè)及HE染色于造模后12周進(jìn)行檢測(cè)。超聲心動(dòng)圖檢測(cè)以下指標(biāo):左室舒張末期內(nèi)徑(LVIDd)、左室收縮末期內(nèi)徑(LVIDs)、左室射血分?jǐn)?shù)(LVEF)和左室短軸縮短率(LVFS)。HE染色觀察偽手術(shù)組和心衰組大鼠心肌組織形態(tài)學(xué)特點(diǎn)。心功能檢測(cè)完畢的大鼠,開胸取心臟,置于提前預(yù)冷的4℃生理鹽水中,經(jīng)主動(dòng)脈灌流沖洗干凈殘存血液后,分離心房心室,浸泡于4%多聚甲醛固定液中,固定24小時(shí)后常規(guī)脫水,石蠟包埋,心室肌組織切片,厚度為5μm,經(jīng)HE染色,然后鏡下觀察。4.哇巴因誘發(fā)心力衰竭大鼠并發(fā)心律失常模型及心功能測(cè)定取心力衰竭SD大鼠用水合氯醛(30 mg·kg~(-1))腹腔注射麻醉后,仰臥位固定于鼠板上,連接肢體導(dǎo)聯(lián),記錄大鼠Ⅱ?qū)?lián)心電圖;同時(shí)通過(guò)右頸總動(dòng)脈插管至左心室腔測(cè)定心功能,并經(jīng)由頸總動(dòng)脈心室插管給藥的方式給予哇巴因(0.4 mg·kg~(-1))制備心力衰竭大鼠并發(fā)急性心律失常模型,NCX-2D2抗體(40、60μg·kg~(-1))、胺碘酮(Amiodarone,3mg-kg~(-1))分別于哇巴因注射前5分鐘經(jīng)頸總動(dòng)脈插管給予,觀察給藥后1h期前收縮次數(shù)、室速和室顫發(fā)生率、持續(xù)時(shí)間的變化;并同步記錄心率、左室最大收縮速率、左室最大舒張速率、左室舒張壓。5.大鼠心室肌細(xì)胞急性分離取健康SD大鼠,50mg·kg~(-1)戊巴比妥鈉腹腔注射麻醉后,頸動(dòng)脈放血后,快速開胸取心臟,修剪后經(jīng)主動(dòng)脈逆行插管懸掛于Langendorff灌流裝置上,以無(wú)鈣且100%氧氣的臺(tái)氏液灌流心臟8～10分鐘,灌注環(huán)境:恒壓(75 cmH2O)、恒溫(37℃),后改為膠原酶液(0.07-0.1 g·L-1)循環(huán)灌流15～20分鐘,觀測(cè)心臟肌組織變大、變軟,冠脈血管邊緣不清時(shí)迅速剪下左心室,用KB液快速?zèng)_洗后置于其中,眼科剪剪至2～3mm3小塊,用玻璃吸管(尖端圓潤(rùn),以免損傷肌細(xì)胞)輕輕吹打3～5 min后即可。過(guò)濾,棄去殘留心臟組織,濾液置于KB液中保存,后將其置于常溫穩(wěn)定3小時(shí)后使用。6.全細(xì)胞膜片鉗記錄應(yīng)用全細(xì)胞膜片鉗技術(shù),在電壓鉗模式下記錄大鼠左心室肌細(xì)胞L-型鈣電流(ICa-L),Na+/Ca2+交換電流(INa/Ca);在電流鉗模式下記錄大鼠左心室肌細(xì)胞動(dòng)作電位(AP),施加條件刺激(15 ms 3Hz)誘發(fā)延遲后除極。結(jié)果:1.NCX-2D2抗體對(duì)哇巴因誘發(fā)大鼠心律失常具有顯著抑制作用(1)10 μg·ml~(-1) NCX-2D2抗體可明顯抑制哇巴因誘發(fā)大鼠離體心臟心律失常的發(fā)生,在哇巴因組,在給藥30min內(nèi)100%大鼠發(fā)生室速,71.43%大鼠出現(xiàn)室顫,在給予10μg·ml~(-1) NCX-2D2抗體干預(yù)后,在觀察期(30min)內(nèi)大鼠室速和室顫發(fā)生率分別降低至28.5%和0,室速持續(xù)時(shí)間由(192.71±18.45)s縮短至(11.85±20.27)s(P0.05),室性期前收縮個(gè)數(shù)由303±26減少至78±7(P0.05)。(2)NCX-2D2抗體可明顯抑制哇巴因誘發(fā)麻醉大鼠心律失常的發(fā)生。在哇巴因組,在給藥后1小時(shí)內(nèi)100%大鼠發(fā)生室速,62.5%大鼠出現(xiàn)室顫。在預(yù)先5分鐘給予60、80μg·kg~(-1)NCX-2D2抗體干預(yù)后,在觀察期(1h)內(nèi)大鼠室速發(fā)生率分別降低為50%、37.5%,室速持續(xù)時(shí)間由(50.91±3.58)min分別縮短至(4.29±4.78)、(0.14±0.21)min(P0.05),大鼠室顫發(fā)生率分別降低為33.3%、0,60μg·kg~(-1) NCX-2D2 抗體使室顫持續(xù)時(shí)間由(2.83±3.03)min 縮短至(0.37±0.58)min(P0.05)。經(jīng)比較發(fā)現(xiàn),80 μg·kg~(-1)NCX-2D2抗體對(duì)哇巴因誘發(fā)心律失常的抑制作用與陽(yáng)性對(duì)照組胺碘酮效果相似。2.腹主動(dòng)脈縮窄術(shù)后12周,大鼠心力衰竭模型制備成功由M型超聲心動(dòng)圖及HE染色發(fā)現(xiàn),大鼠腹主動(dòng)脈縮窄術(shù)后12周,大鼠出現(xiàn)心力衰竭。M型超聲心動(dòng)圖顯示,大鼠左室收縮末期內(nèi)徑和左室舒張末期內(nèi)徑均明顯增大,左室收縮末期內(nèi)徑由(2.05±0.08)mm增大至(5.42±0.29)mm(P0.05),左室舒張末期內(nèi)徑由(5.25±0.19)mm增大至(7.59±0.36)mm(P0.05);左室射血分?jǐn)?shù)由(92±1.37)%減小至(62±5.65)%(P0.05),左室短軸縮短率由(58±2.48)%減小至(30±2.85)%(P0.05)。HE染色顯示,心力衰竭大鼠細(xì)胞排列紊亂,心肌細(xì)胞出現(xiàn)肥大,部分心肌組織出現(xiàn)纖維化。3.NCX-2D2抗體對(duì)哇巴因誘發(fā)心力衰竭大鼠并發(fā)的心律失常具有顯著抑制作用研究結(jié)果顯示,0.4 mg·kg~(-1)哇巴因可明顯增強(qiáng)心力衰竭大鼠心功能,但同時(shí)誘發(fā)出嚴(yán)重的心律失常。預(yù)先給予40、60μg·kg~(-1) NCX-2D2抗體干預(yù)后,哇巴因誘發(fā)心衰大鼠并發(fā)的心律失常被明顯抑制,且大鼠心功能較心衰組明顯提高。在哇巴因組100%大鼠發(fā)生室速,66.7%大鼠發(fā)生室顫,在給予哇巴因前5 min給予40、60μg·kg~(-1) NCX-2D2抗體干預(yù)后,在觀察期(1h)內(nèi)室速發(fā)生率分別降低至66.7%和33.3%,在給予哇巴因前5 min給予40、60μg·kg~(-1) NCX-2D2抗體干預(yù)后,室速發(fā)生率分別降低至66.7%和33.3%,室速持續(xù)時(shí)間由(1120.8±173.9)s分別縮短至(264.6±206.4)、(8.6±13.5)s(P0.05),室顫發(fā)生率分別降低至 33.3%和 16.7%,室顫持續(xù)時(shí)間由(22.50±24.31)s 分別縮短至(3.70±6.10)、(1.50±3.67)s(P0.05),室性期前收縮個(gè)數(shù)由1640±157分別降低至488±19和138±33(P0.05)。經(jīng)比較發(fā)現(xiàn),60μg·kg~(-1) NCX-2D2抗體對(duì)室性期前收縮的抑制作用較陽(yáng)性對(duì)照組胺碘酮明顯,對(duì)其他類型心律失常的抑制作用與陽(yáng)性對(duì)照組胺碘酮相似,且其心功能較心衰組大鼠明顯提高。4.NCX-2D2抗體可部分逆轉(zhuǎn)哇巴因?qū)Υ笫髥蝹�(gè)心室肌細(xì)胞鈉-鈣交換電流(INa/Ca)的增大作用在鉗制電位+50mV和-100mV時(shí),哇巴因組心肌細(xì)胞INa/Ca分別為9.20±0.09和-11.42±0.27(pA/pF),與對(duì)照組 4.25±0.05 和-4.08±0.09(pA/pF)相比明顯增大(P0.05)。在哇巴因存在的情況下聯(lián)合給予5μg·ml~(-1)NCX-2D2抗體后,INa/Ca在+50mV和-100mV時(shí)的外向和內(nèi)向電流分別降低至6.67±0.27和-7.42±0.26(pA/pF),均明顯低于哇巴因組(P0.05),但仍未完全恢復(fù)至正常水平(P0.05)。5.NCX-2D2抗體可部分逆轉(zhuǎn)哇巴因?qū)Υ笫髥蝹�(gè)心室肌細(xì)胞L-型鈣電流(ICa-L)的增大作用研究結(jié)果顯示,哇巴因組心肌細(xì)胞ICa-L為-8.73±0.36(pA/pF),與對(duì)照組-6.30±0.53(pA/pF)相比明顯增大(P0.05)。在聯(lián)合應(yīng)用5μg·ml~(-1) NCX-2D2抗體后,ICa-L降至-7.45±0.29(pA/pF),與哇巴因組相比明顯降低(P0.05),但仍未完全恢復(fù)至正常水平(P0.05)。6.NCX-2D2抗體可顯著抑制哇巴因誘發(fā)的大鼠單個(gè)心室肌細(xì)胞延遲后除極研究結(jié)果顯示,對(duì)照組和2D2抗體組均未出現(xiàn)延遲后除極(DADs)。哇巴因組大鼠單個(gè)心室肌細(xì)胞DADs發(fā)生率為83.33%,在給予5μg·ml~(-1)NCX-2D2抗體干預(yù)后,大鼠單個(gè)心室肌細(xì)胞DADs發(fā)生率降低為8.3%。與哇巴因組相比,抗體干預(yù)組(哇巴因+2D2抗體組)大鼠單個(gè)心室肌細(xì)胞DADs發(fā)生率明顯降低(P0.05)。結(jié)論:NCX-2D2抗體可顯著抑制哇巴因誘發(fā)正常及心力衰竭大鼠并發(fā)的心律失常,其抗心律失常機(jī)制主要與抑制鈉-鈣交換和L-型鈣通道以減輕心肌細(xì)胞鈣超載和抑制心肌細(xì)胞延遲后除極有關(guān)。
[Abstract]:Objective: to establish an arrhythmia model of normal and heart failure rats induced by ouabain, observe the effect of anti sodium calcium exchange NCX-2D2 antibody on the arrhythmia of model rats, and analyze its possible mechanism. Methods: 1. ouabain induced adult rat in vitro and in vivo cardiac arrhythmia model (1) ouabain induced rat in vitro Cardiac arrhythmia model healthy SD rats, 50 mg. Kg~ (-1) pentobarbital sodium intraperitoneal injection anaesthesia, open the chest free heart and hang on the Langendorff device, the aorta retrograde perfusion, the flow rate of 8mL min-1, observe at least 30 min after the electrocardiogram wave stability after the use of drug pump administration, record electrocardiogram. Experimental groups are as follows: 1 normal group: 1 normal Control group: the irrigation of table's solution containing 2.5 mmol / L-1 CaCl2; (2) 2D2+CaCl2 group: 10 micron g / ml~ (-1) NCX-2D2 antibody and 2.5 mmol L-1 CaCl2 liquid perfusion. Uabain and 2.5 mmol.L-1 CaCl2's liquid perfusion. Electrocardiogram recorded the number of ventricular premature contractions, ventricular tachycardia and ventricular fibrillation in 30 min after drug intervention. (2) ouabain induced arrhythmia model healthy SD rats were placed on the rat board with 30 mg kg~ (-1) chloral chloral abdominal cavity injection. The BL-420F biological function test system was used to record the electrocardiogram of rat II lead, and the 30min electrocardiogram was continuously observed without abnormal tail vein. The number of ventricular premature contraction in 1 h after drug intervention, the ventricular tachycardia and the duration of ventricular fibrillation and the heart failure model of.2. rats were prepared for the preparation of adult healthy SD rats. The rats were divided into the puppet group and the heart failure group, 24 h before the operation, the weight of the rats were weighed and the chloral hydrate (30 mg. Kg~ (-1)) was given intraperitoneal injection. After the rats were anesthetized, the rats were fixed on the rat plate and removed the hair of the rat abdomen. The longitudinal incision after the left rib angle of the rat was 2 cm, the abdominal aorta was exposed by blunt separation, and the needle head of the 7 needle and the abdominal aorta were separated. Ligation, and then draw out the needle to form the abdominal aorta stenosis and close the abdominal cavity. The pseudo operation group only did not ligate the abdominal aorta, and the rest of the operation were the same as the heart failure group. 3 days after the operation, the celiac injection of penicillin 200 thousand units to prevent infection.3. echocardiography and HE staining at 12 weeks after the operation. The following index of the echocardiography: left ventricle: left ventricle The end diastolic diameter (LVIDd), the left ventricular end systolic diameter (LVIDs), the left ventricular ejection fraction (LVEF) and the short axis shortening rate (LVFS).HE staining were used to observe the histomorphological characteristics of the myocardium of the rats in the PN group and the heart failure group. The rats after the cardiac function test were taken into the heart by opening the chest, and placed in the pre cooled 4 centigrade normal saline, and irrigated through the aorta. After a clean and residual blood, the atrial ventricle was separated and soaked in 4% polyformaldehyde fixed solution. After 24 hours fixed dehydration, paraffin embedded and ventricular muscle tissue section, the thickness was 5 mu m, and HE staining was used to observe the arrhythmia model of heart failure induced by.4. ouabain and the cardiac function determination of heart failure SD rats with chlorinated chloride. After intraperitoneal injection of aldehyde (30 mg. Kg~ (-1)), the supine position was fixed on the rat plate, connected to the limb lead, and recorded the electrocardiogram of the rat II lead. At the same time, the cardiac function was measured by the right common carotid artery intubation to the left ventricle and ouabain (0.4 mg. Kg~ (-1)) was given by the way of the ventricular catheterization of the common carotid artery to prepare the acute heart failure rats. The arrhythmia model, NCX-2D2 antibody (40,60 g / kg~ (-1)) and amiodarone (Amiodarone, 3mg-kg~ (-1)) were given respectively by the common carotid artery intubation 5 minutes before ouabain injection. The number of pre systolic times, the rate of ventricular tachycardia and ventricular fibrillation, the duration of duration were observed, and the heart rate, the maximum systolic velocity of left ventricle and the maximum left ventricular diastolic speed were recorded simultaneously. Rate, left ventricular diastolic pressure.5. rat ventricular myocytes were isolated from healthy SD rats. After intraperitoneal injection of 50mg. Kg~ (-1) pentobarbital sodium, the heart was quickly opened after the carotid artery bleed. After pruning, the aortic retrograde intubation was suspended on the Langendorff perfusion device and perfusion of the heart without calcium and 100% oxygen for 8~10 minutes. Environment: constant pressure (75 cmH2O), constant temperature (37 degrees C), then converted to collagenase fluid (0.07-0.1 G. L-1) for 15~20 minutes. The observation of cardiac muscle tissue becomes larger and softer. The left ventricle is quickly cut off when the coronary artery is not clear. After rapid flushing of the KB solution, the eye section is cut to 2 to 3mm3 small pieces, and the glass tube is rounded to avoid injury of muscle fine. After blowing 3~5 min gently, the cells were filtered and abandoned to the residual cardiac tissue, the filtrate was stored in the KB solution, and then the whole cell patch clamp technique was used to record the whole cell patch clamp technique using the whole cell patch clamp of.6. after 3 hours at normal temperature, and the L- type calcium current (ICa-L) and Na+/Ca2+ exchange current (INa/Ca) were recorded in the rat left ventricular myocytes under the voltage clamp mode. The action potential (AP) of rat left ventricular myocytes (AP) was recorded under current clamp mode, and conditioned stimulation (15 ms 3Hz) induced depolarization. Results: 1.NCX-2D2 antibody had significant inhibitory effect on ouabain induced arrhythmia induced by ouabain (1) 10 mu g. Ml~ (-1) NCX-2D2 antibody could obviously inhibit the hair cardiac arrhythmia induced by ouabain. In ouabain group, 100% rats in ouabain group had ventricular tachycardia and 71.43% rats had ventricular fibrillation. The rate of ventricular tachycardia and ventricular fibrillation was reduced to 28.5% and 0 in the observation period (30min). The duration of ventricular tachycardia was shortened from (192.71 + 18.45) s to (11.85 + 20.27) s (P0.05) and ventricular premature contraction in the observation period (30min). The rate of ventricular tachycardia was reduced to 28.5% and 0 in the observation period (30min). The number decreased from 303 + 26 to 78 + 7 (P0.05). (2) NCX-2D2 antibody could obviously inhibit the occurrence of arrhythmia in ouabain induced rats. In ouabain group, the ventricular tachycardia occurred in 100% rats in 1 hours after administration, and ventricular fibrillation in 62.5% rats. 60,80 uh G. Kg~ (-1) NCX-2D2 antibody was given in advance for 5 minutes, and the rat ventricular tachycardia occurred in the observation period (1H). The rate was reduced to 50%, 37.5%, and the duration of room speed was shortened from (50.91 + 3.58) min to (4.29 + 4.78), (0.14 + 0.21) min (P0.05), and the incidence of ventricular fibrillation in rats was reduced to 33.3%, and 0,60 mu g. Kg~ (-1) NCX-2D2 antibody shortened the duration of ventricular fibrillation from (2.83 + 3.03) min to (0.37 + 0.58) min (P0.05). The inhibitory effect of antibody on ouabain induced arrhythmia was similar to that of positive control histamine iodide. 12 weeks after.2. abdominal aorta coarctation, the rat model of heart failure was successfully prepared by M echocardiography and HE staining, 12 weeks after the abdominal aorta coarctation in rats. The rats had heart failure.M echocardiography, and the left ventricle of rats The end systolic diameter and left ventricular end diastolic diameter increased significantly. The end-stage internal diameter of left ventricular systole increased from (2.05 + 0.08) mm to (5.42 + 0.29) mm (P0.05). The end diastolic diameter of left ventricle increased from (5.25 + 0.19) mm to (7.59 + 0.36) mm (P0.05), and left ventricular ejection fraction decreased from (92 + 1.37)% to (62 5.65)% (P0.05), and the short axis shortening rate of left ventricle was (58 + 5.25). % to (30 + 2.85)% (P0.05)% (P0.05).HE staining showed that the cells in the heart failure rats were arranged in disorder, the cardiac myocytes appeared hypertrophy, and some myocardial tissue appeared fibrosis.3.NCX-2D2 antibody. The results showed that 0.4 mg. Kg~ (-1) wow Ba could obviously enhance the heart of heart failure induced arrhythmia in rats. The heart function of the rats was induced by force, but the cardiac arrhythmia was induced at the same time. The prognosis of 40,60 mu g. Kg~ (-1) NCX-2D2 antibody was given in advance. The arrhythmia in the rats induced by ouabain induced heart failure was obviously inhibited, and the heart function of the rats was significantly higher than that in the heart failure group. In ouabain group, 100% rats had ventricular tachycardia, and the 66.7% rats had ventricular fibrillation and were given wow. The prognosis of 40,60 mu g. Kg~ (-1) NCX-2D2 antibody was given to the first 5 min of Ba, and the rate of ventricular tachycardia in the observation period (1H) decreased to 66.7% and 33.3% respectively. The rate of ventricular tachycardia decreased to 66.7% and 33.3%, respectively, and the duration of ventricular tachycardia was reduced to (264.6. 173.9) to 264.6 min before giving ouabain. (8.6 + 13.5) s (P0.05), the incidence of ventricular fibrillation was reduced to 33.3% and 16.7% respectively. The duration of ventricular fibrillation was shortened from (22.50 + 24.31) s to (3.70 + 6.10), (1.50 + 3.67) s (P0.05). The number of ventricular premature contraction decreased from 1640 + 157 to 22.50 + 24.31 and P0.05. The inhibitory effect of contraction was more obvious than that of the positive control histamine iodide, and the inhibitory effect on other types of arrhythmia was similar to that of the positive control histamine iodide, and the heart function was significantly higher than that of the heart failure group. The.4.NCX-2D2 antibody could partly reverse the effect of ouabain on the increase of sodium calcium exchange current (INa/Ca) in single ventricular myocytes of rats. The INa/Ca of cardiac myocytes in ouabain group was 9.20 + 0.09 and -11.42 + 0.27 (pA/pF), respectively, compared with 4.25 + 0.05 and -4.08 + 0.09 (pA/pF) in the control group (P0.05). Under the presence of ouabain 5 u g ml~ (-1) NCX-2D2 antibodies, the extroverted and introverted currents were reduced respectively. 6.67 + 0.27 and -7.42 + 0.26 (pA/pF) were significantly lower than ouabain group (P0.05), but still not completely recovered to normal level (P0.05).5.NCX-2D2 antibody could partly reverse the effect of ouabain on the increase of L- type calcium current (ICa-L) in rat single ventricular myocytes. The myocardial ICa-L in ouabain group was -8.73 + 0.36 (pA/pF), and control Group -6.30 + 0.53 (pA/pF) was significantly increased (P0.05). After combined use of 5 g. Ml~ (-1) NCX-2D2 antibody, ICa-L decreased to -7.45 + 0.29 (pA/pF), compared with ouabain group (P0.05), but still not completely recovered to normal level (P0.05) could significantly inhibit the depolarization of rat single ventricular myocytes induced by ouabain. The results showed that there was no delayed depolarization (DADs) in the control group and the 2D2 antibody group. The incidence of DADs in single ventricular myocytes in ouabain group was 83.33%. The incidence of DADs in single ventricular myocytes in rats was reduced to 8.3%. compared to ouabain group, and the antibody intervention group (ouabain +2D2 antibody group) was compared with 5 g. Ml~ (-1) NCX-2D2 antibody. The incidence of DADs in rat single ventricular myocytes was significantly decreased (P0.05). Conclusion: NCX-2D2 antibody can significantly inhibit the arrhythmia induced by ouabain and normal and heart failure rats. Its antiarrhythmic mechanism is mainly related to the inhibition of sodium calcium exchange and L- type calcium channel to reduce myocardial cell calcium overload and inhibit myocardial cell delay. Close.

【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R541

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 陳偉偉;高潤(rùn)霖;劉力生;朱曼璐;王文;王擁軍;吳兆蘇;李惠君;顧東風(fēng);楊躍進(jìn);鄭哲;蔣立新;胡盛壽;;《中國(guó)心血管病報(bào)告2015》概要[J];中國(guó)循環(huán)雜志;2016年06期

2 孫瑤;張嬋;簡(jiǎn)潔;;九龍?zhí)倏傸S酮調(diào)控自噬對(duì)抗心肌缺血/再灌注損傷的實(shí)驗(yàn)研究[J];中國(guó)藥理學(xué)通報(bào);2015年02期

3 賀永貴;李王芳;伊紅麗;鄭桓;習(xí)瑾昆;;黃芪甲苷抑制GSK-3β活性介導(dǎo)大鼠心肌缺血/再灌注損傷作用的線粒體機(jī)制研究[J];中國(guó)藥理學(xué)通報(bào);2014年03期

4 李濤;曾曉榮;;鈉鈣交換體與心臟疾病的研究進(jìn)展[J];瀘州醫(yī)學(xué)院學(xué)報(bào);2014年01期

5 劉浩宇;常廣磊;段芹;張冬穎;;心血管疾病患者死亡原因分析[J];重慶醫(yī)學(xué);2013年27期

6 邵瑩;吳啟南;周婧;樂巍;巢建國(guó);;淡竹葉黃酮對(duì)大鼠心肌缺血/再灌注損傷的保護(hù)作用[J];中國(guó)藥理學(xué)通報(bào);2013年02期

7 林晨暉;李源;王焱;;心肌細(xì)胞鈉鈣交換體研究進(jìn)展[J];實(shí)用心腦肺血管病雜志;2011年01期

8 王波;;鈉鈣交換體對(duì)心肌保護(hù)作用的研究進(jìn)展[J];西安文理學(xué)院學(xué)報(bào)(自然科學(xué)版);2009年03期

9 沈磊;吳玉林;;鈉鈣交換體及其抑制劑在心律失常中的作用[J];中國(guó)臨床藥理學(xué)與治療學(xué);2006年06期

10 劉秀華;鈉鈣交換體與心肌缺血再灌注[J];中國(guó)動(dòng)脈硬化雜志;2005年02期

，

本文編號(hào)：1775833