發(fā)布時間：2018-01-08 15:23

  本文關(guān)鍵詞：β受體阻滯劑治療后心率下降不同程度對心力衰竭大鼠的影響　出處：《河北醫(yī)科大學(xué)》2016年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 心力衰竭 β受體阻滯劑 心率 β_1腎上腺素受體mRNA β_1腎上腺素受體蛋白表達(dá)

【摘要】：心力衰竭是各種類型心臟疾病的嚴(yán)重和終末階段。在全球范圍內(nèi),心力衰竭已經(jīng)成為一個日益增長的健康問題,并且隨著年齡的增加,發(fā)病率也不斷上升。心力衰竭早期,心排血量降低,反射性地使交感神經(jīng)系統(tǒng)興奮性增加、心率加快。在一定范圍內(nèi),心率加快可以使心輸出量增加,然而心率增快超過一定范圍時,心肌耗氧量增加、心室舒張期顯著縮短、冠脈血流減少,從而加重心力衰竭。臨床實(shí)驗(yàn)表明,靜息心率每分鐘增加5次,心血管死亡和心力衰竭住院的風(fēng)險增加16%。β-受體(β-adrenergic receptor,β-AR)阻滯劑通過阻斷β_1腎上腺素能受體(β_1-adrenergic receptor,β_1-AR),減慢心率,降低心肌耗氧量,改善心室充盈功能,改善心力衰竭患者的心功能和預(yù)后。本課題組前期的基礎(chǔ)實(shí)驗(yàn)研究結(jié)果證實(shí)β_1-AR阻滯劑能夠降低射血分?jǐn)?shù)(EF)40%的心力衰竭大鼠的心率、上調(diào)β_1-AR mRNA表達(dá)水平、改善心功能參數(shù)。但是,心率降低和β_1-ARmRNA表達(dá)水平升高到一定程度,心功能并未得到進(jìn)一步改善。此外,有研究顯示在LVEF≥50%和LVEF50%的心肌梗死患者中,β-AR阻滯劑的治療可以降低患者的死亡率。本課題研究心率下降不同程度時,心肌梗死后心力衰竭(40%≤EF60%)大鼠的心功能、左室質(zhì)量指數(shù)(LVMI)、β_1-AR mRNA表達(dá)和蛋白表達(dá)水平的變化情況。探討心率下降不同程度對心肌梗死后心力衰竭大鼠的心功能的影響。目的:研究β_1-AR阻滯劑使心率下降不同程度與心肌梗死后心力衰竭大鼠的心功能、LVMI、β_1-AR mRNA表達(dá)及蛋白表達(dá)變化的關(guān)系。方法:心肌梗死后心力衰竭大鼠模型制備采取的是手術(shù)結(jié)扎心臟冠狀動脈左前降支的方法,假手術(shù)組大鼠單純開胸,并不結(jié)扎冠狀動脈。全部大鼠均于手術(shù)后4周實(shí)施超聲心動圖(UCG)檢查,判定心力衰竭模型成功的標(biāo)準(zhǔn)是超聲結(jié)果顯示40%≤EF60%。手術(shù)后4周共有25只大鼠的超聲結(jié)果符合心力衰竭的標(biāo)準(zhǔn),根據(jù)β_1-AR阻滯劑治療后心率下降的不同水平隨機(jī)分為4組:G0組:心力衰竭對照組;G1組:心率下降35-45次/分;G2組:心率下降75-85次/分;G3組:心率下降115-125次/分。G0組和假手術(shù)組的大鼠均給予等容積的生理鹽水灌胃,G1、G2和G3組大鼠均予以富馬酸比索洛爾片灌胃,全部大鼠在達(dá)到目標(biāo)心率后繼續(xù)灌胃6周,6周后實(shí)施UCG檢查。取材時測定大鼠左室心肌重量,計算LVMI。采用反轉(zhuǎn)錄-聚合酶鏈?zhǔn)椒磻?yīng)(Reverse reaction PCR,RT-PCR)測定大鼠左心室非梗死區(qū)的心肌β_1-AR mRNA表達(dá)水平,使用蛋白質(zhì)印跡法(Western Blot)檢測大鼠左心室非梗死區(qū)心肌β_1-AR蛋白表達(dá)水平。結(jié)果:1超聲心動圖結(jié)果UCG檢查分別在造模術(shù)后4周、富馬酸比索洛爾片治療6周后實(shí)施,以檢測心功能指標(biāo)。造模術(shù)后4周,G0、G1、G2和G3組大鼠的LVEDD、LVESD較假手術(shù)組增加,FS和EF較假手術(shù)組減低,差異均有統(tǒng)計學(xué)意義(P0.01)。與假手術(shù)組對比,G0、G1、G2和G3組大鼠的LVPWd、IVSd增加,差異有統(tǒng)計學(xué)意義(P0.05)。藥物治療前,G0、G1、G2和G3組大鼠UCG數(shù)據(jù)間均無統(tǒng)計學(xué)差異(P0.05)。富馬酸比索洛爾片持續(xù)灌胃6周后,G1、G2組的FS、EF較G0組增高,差異有統(tǒng)計學(xué)意義(P0.05)。G3組的FS、EF與G0組相比,差異無統(tǒng)計學(xué)意義(P0.05)。與G0組相比,G1、G2組的LVEDD、LVESD有一定的改善,差異有統(tǒng)計學(xué)意義(P0.01)。G3組的LVEDD、LVESD與G0組相比,差異無統(tǒng)計學(xué)意義(P0.05)。G1、G2和G3組的IVSd、LVPWd與G0組相比,差異無統(tǒng)計學(xué)意義(P0.05)。2心率與血壓變化給藥前,采用MD3000型生物信號采集系統(tǒng)經(jīng)鼠尾動脈測定全部大鼠的心率和血壓。給藥前,G1、G2、G3組與G0組大鼠的心率和血壓水平相似,差異無統(tǒng)計學(xué)意義(P0.05)。比索洛爾灌胃6周后,G1組、G2組及G3組的大鼠心率分別下降了45.00±6.99次/分、78.83±7.60次/分、119.50±10.33次/分,差異有統(tǒng)計學(xué)意義(P0.01)。比索洛爾灌胃6周后,與G0組對比,G1組、G2組及G3組的血壓水平的差異無統(tǒng)計學(xué)意義(P0.05)。3心室質(zhì)量指數(shù)(LVMI)G1、G2、G3組大鼠的LVMI較G0組有所下降(P0.01),卻仍高于假手術(shù)組(P0.05),差異有統(tǒng)計學(xué)意義。4非梗死區(qū)心肌組織β_1-AR mRNA和蛋白表達(dá)G0組大鼠的非梗死區(qū)心肌β_1-AR mRNA、蛋白表達(dá)水平低于假手術(shù)組,差異有統(tǒng)計學(xué)意義(P0.01)。藥物治療后,G1、G2組大鼠β_1-AR mRNA、蛋白表達(dá)水平較G0組升高(P0.01),但是仍低于假手術(shù)組(P0.01);G1與G2組的β_1-AR mRNA、蛋白表達(dá)水平無統(tǒng)計學(xué)差異(P0.05)。與G0組相比,G3組的β_1-AR mRNA升高,差異無統(tǒng)計學(xué)意義(P0.05),G3組的β_1-AR蛋白表達(dá)增加,差異有統(tǒng)計學(xué)意義(P0.01)。與G1和G2組比較,G3組β_1-AR mRNA、蛋白表達(dá)水平減低,差異有統(tǒng)計學(xué)意義(P0.05)。結(jié)論:心率降低35-45次/分組、75-85次/分組,不僅心功能有所改善,而且β_1-AR mRNA、蛋白表達(dá)也有所上調(diào);然而心率持續(xù)降低,即心率降低115-125次/分組,心功能未見進(jìn)一步改善,且β_1-AR mRNA、蛋白表達(dá)雖有所上調(diào),仍低于心率降低35-45次/分組、75-85次/分組。
[Abstract]:Heart failure is of various types of heart disease and severe end stage. In the global scope, heart failure has become a growing health problem, and with the increase of age, the incidence is rising. The early stage of heart failure, cardiac output decreased, reflecting the increased excitability of the sympathetic nervous system, heart rate. Within a certain range, can make the heart rate, cardiac output increased, but the heart rate increased by more than a certain range, increased myocardial oxygen consumption, ventricular diastolic coronary blood flow decreased significantly shortened, thus increase the heart failure. The clinical experiments showed that resting heart rate increased 5 times per minute, the risk of cardiovascular death and heart failure hospitalization increased 16%. beta (-adrenergic beta receptor, -AR beta blockers) by blocking beta adrenergic receptor _1 (beta _1-adrenergic beta receptor, _1-AR), slow heart rate, reduce myocardial oxygen consumption, The improvement of ventricular filling function, improve cardiac function and prognosis of heart failure patients. Results the experimental study confirmed previous beta blockers can reduce _1-AR ejection fraction (EF) in rats with heart failure 40% heart rate, increase the expression level of mRNA beta _1-AR, improve heart function parameters. However, the heart rate decreased and the expression of _1-ARmRNA beta the level is increased to a certain extent, the heart function has not been improved. In addition, studies have shown that in patients with myocardial infarction LVEF = 50% and LVEF50% in the treatment of -AR beta blockers can reduce the mortality of patients. This study decreased heart rate, heart failure after myocardial infarction (40% EF60%) on heart function in rats, left ventricular mass index (LVMI), mRNA expression of _1-AR and protein expression levels. The study of heart rate decreased in different degree of heart failure after myocardial infarction in rats with heart function. Ring. Objective: To study the _1-AR beta blockers to heart rate, decreased with heart failure after myocardial infarction in rats LVMI, mRNA expression and protein expression of _1-AR. Methods: the relationship between the change of heart failure after myocardial infarction rat model is taken by the descending branch of the coronary artery ligating left anterior, false the rats of operation group received open chest, no ligation of coronary artery. All the rats were 4 weeks after surgery the implementation of echocardiography (UCG) examination, to determine the heart failure model of success is ultrasound ultrasound showed 40% EF60%. 4 weeks after surgery there were 25 rats with heart failure results according to different standards. The level of _1-AR were randomly divided into beta blockers in the treatment of heart rate falling into 4 groups: group G0: control group G1 group: heart failure; heart rate decreased 35-45 beats per minute; group G2: heart rate decreased 75-85 beats per minute; group G3:.G0 group decreased heart rate 115-125 times / min And the rats in sham operation group were given normal saline by gavage, G1, G2 and G3 group rats were given intragastric administration of Bisoprolol Fumarate Tablets, all the rats to gavage for 6 weeks to reach the target heart rate after 6 weeks after the implementation of UCG. Determination of left ventricular myocardium of rats were weight, calculated LVMI. using reverse transcription polymerase chain reaction (Reverse reaction PCR, RT-PCR) were non infarcted left ventricular myocardium _1-AR beta mRNA expression using Western blotting (Western Blot) detection of left ventricle in rats the expression of myocardial infarction _1-AR protein. Results: 1 the results of echocardiography examination respectively in UCG model 4 weeks after operation, Bisoprolol Fumarate Tablets after 6 weeks of treatment, in order to detect the indexes of heart function modeling. After 4 weeks, G0, G1, G2 and G3 group rats LVEDD, LVESD increased compared with sham group, FS and EF compared with the sham operation group decreased, the differences were statistically. 涔，

本文編號：1397661