本文選題：心肌梗死 + 美托洛爾��； 參考：《南方醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景:心血管病死亡占我國(guó)居民總死亡原因的首位,心肌梗死(MI)后并發(fā)的室顫等惡性心律失常是引起心臟性猝死(SCD)的主要原因。目的:探討琥珀酸美托洛爾早期干預(yù)對(duì)兔心肌梗死40天后心臟組織縫隙連接重構(gòu)以及細(xì)胞凋亡的影響。方法:將24只成年雄性新西蘭大白兔隨機(jī)分成假手術(shù)組(SH組,n=6)、心肌梗死組(MI組,n=6)、心梗后早期干預(yù)組(EBMI組,n=6)和心梗后常規(guī)干預(yù)組(RBMI組,n=6),通過(guò)結(jié)扎冠狀動(dòng)脈前降支建立心肌梗死模型,假手術(shù)組不結(jié)扎血管,余操作均相同。EBMI組和RBMI組分別于麻醉清醒后和心梗24小時(shí)后以琥珀酸美托洛爾(12.5mg/kg,溶于2ml蒸餾水)灌胃,SH組和MI組以等量蒸餾水灌胃。術(shù)后6小時(shí),以生物化學(xué)法檢測(cè)血清心肌壞死標(biāo)志物(血清乳酸脫氫酶和肌酸激酶)水平。術(shù)后40天開胸暴露心臟,通過(guò)雙極起搏電極測(cè)定心室顫動(dòng)閾值;以免疫熒光法觀察縫隙連接蛋白43(Cx43)及其磷酸化(p-Cx43)和縫隙連接蛋白45(Cx45)在心室肌組織的分布情況,TUNEL法測(cè)定心肌細(xì)胞凋亡率,Western blot法檢測(cè)心室肌組織Cx43、p-Cx43、Cx45和Bcl-2、Bax、Caspase-3蛋白表達(dá)水平;實(shí)時(shí)熒光定量PCR法測(cè)定心肌組織中Cx43及Cx45的mRNA表達(dá)水平。結(jié)果:1、心肌梗死組的血清乳酸脫氫酶和肌酸激酶水平均高于假手術(shù)組(P均0.01);2、MI組的心室顫動(dòng)閾值低于SH組(P0.05),EBMI組和RBMI組心室顫動(dòng)閾值均高于MI組(P均0.05)。3、縫隙連接蛋白在心室肌的分布情況:SH組、EBMI組和RBMI組可見(jiàn)CX43主要位于閏盤內(nèi),與細(xì)胞長(zhǎng)軸垂直,呈線狀排列,而側(cè)向分布的Cx43相對(duì)較少,MI組則相反;p-Cx43和Cx45的分布表現(xiàn)與Cx43相似。4、心肌組織中縫隙連接蛋白的表達(dá):(1)蛋白表達(dá)水平:MI組p-Cx43和Cx45表達(dá)水平以及p-Cx43/Cx43比例均低于SH組(P均0.05);EBMI組和RBMI組p-Cx43和Cx45表達(dá)水平以及p-Cx43/Cx43比例均高于MI組(P均0.05),且EBMI組高于RBMI組(P0.05);各組CX43總蛋白的灰度分析無(wú)統(tǒng)計(jì)學(xué)差異(P0.05)。(2)mRNA表達(dá)水平:MI組Cx43和Cx45的mRNA表達(dá)水平低于SH組(P均0.05);EBMI組和RBMI組Cx43和Cx45的mRNA表達(dá)水平均高于MI組(P均0.05),且EBMI組高于RBMI組(P0.05)。5、凋亡相關(guān)檢測(cè):(1)TUNEL法:MI組心肌細(xì)胞凋亡率明顯高于SH組(P0.05),EBMI組和RBMI組的心肌細(xì)胞凋亡率低于MI組(P均0.05),且EBMI組低于RBMI組(P0.05);(2)凋亡相關(guān)蛋白表達(dá)水平:MI組的Bcl-2水平及Bcl-2/Bax比值低于SH組(P均0.05),EBMI組和RBMI組的Bcl-2水平及Bcl-2/Bax比值高于MI組(P均0.05),且EBMI組高于RBMI組(P0.05);MI 組的 Bax 和 Caspase-3 水平高于 SH 組(P 均0.05),而 EBMI組和RBMI組的Bax和Caspase-3水平低于MI組(P均0.05),且EBMI組低于 RBMI 組(P0.05)。結(jié)論:琥珀酸美托洛爾通過(guò)改善心梗后心室肌縫隙連接蛋白的空間分布,減少縫隙連接蛋白的降解及去磷酸化,降低心梗后惡性心律失常的易感性,抑制心肌細(xì)胞凋亡,從而對(duì)心肌梗死兔心臟起保護(hù)作用,并且早期給藥獲益更明顯。
[Abstract]:Background: cardiovascular disease is the leading cause of death in China. Malignant arrhythmias such as ventricular fibrillation after myocardial infarction (MI) are the main causes of sudden cardiac death (SCD). Aim: to investigate the effects of early intervention of metoprolol succinate on gap junction remodeling and apoptosis of heart tissue after 40 days of myocardial infarction in rabbits. Methods: Twenty-four adult male New Zealand white rabbits were randomly divided into sham operation group (SH group), myocardial infarction group (MI group), early intervention group (EBMI group) and post myocardial infarction group (RBMI group). Myocardial infarction model, The rest of the procedures were the same in sham operation group. EBMI group and RBMI group were perfused intragastrically with metoprolol succinate 12.5 mg / kg, dissolved in 2ml distilled water, respectively after awake anesthesia and 24 hours after myocardial infarction. The serum levels of lactate dehydrogenase and creatine kinase were measured by biochemical method at 6 hours after operation. The ventricular fibrillation threshold was measured by bipolar pacing electrode 40 days after operation. The distribution of gap junction protein 43 (Cx43) and its phosphorylated protein (p-Cx43) and gap junction protein 45 (Cx45) in ventricular myocytes were observed by immunofluorescence method. Tunel method was used to determine the apoptosis rate of cardiac myocytes. Western blot was used to detect the expression of Cx43 + Cx43 and Bcl-2BaxCaspase-3 in ventricular myocytes. The expression of Cx43 and Cx45 in myocardial tissue was measured by real-time fluorescence quantitative PCR. Results the serum lactate dehydrogenase and creatine kinase levels in the myocardial infarction group were higher than those in the sham operation group (P < 0.01). The ventricular fibrillation threshold in the myocardial infarction group was lower than that in the SH group (P 0.05) and the ventricular fibrillation threshold in the RBMI group was higher than that in the MI group (P < 0.05). In the distribution of ventricular muscle, CX43 was mainly located in intercalated disc in RBMI and EBMI group. Perpendicular to the long axis of the cell. On the contrary, the distribution of p-Cx43 and Cx45 was similar to that of Cx43 in the laterally distributed Cx43 group. The expression level of gap junction protein: 1) in myocardial tissue was lower than that in SH group (P < 0.01). The expression level of p-Cx43 and Cx45 and p-Cx43/Cx43 ratio were lower than those in SH group (P The expression level of p-Cx43 and Cx45 and the ratio of p-Cx43/Cx43 in both groups were higher than those in MI group (P 0.05) and EBMI group (P < 0.05), and the expression of CX43 total protein in EBMI group was higher than that in RBMI group (P < 0.05), and there was no significant difference in the gray level of CX43 total protein expression between the two groups. The mRNA expression levels of Cx43 and Cx45 in the group of RBMI were lower than those in the group of SH-SH. The mRNA expression levels of Cx43 and Cx45 in both groups were higher than those in MI group and RBMI group, and that in EBMI group was higher than that in RBMI group (P 0.05. 5). The apoptosis-related assays showed that the apoptotic rate was significantly higher in group 1: 1 Tunel than that in group SH (P 0.05) and group RBMI (P < 0.05). The apoptotic rate was significantly lower in EBMI group than that in SH group (P 0.05) and RBMI group (P < 0.05). Apoptosis-related protein expression level in EBMI group was lower than that in RBMI group (P 0.05) Bcl-2 level and Bcl-2/Bax ratio were lower in EBMI group than in SH group (P < 0.05). Bcl-2 level and Bcl-2/Bax ratio in RBMI group and RBMI group were higher than those in MI group (P 0.05), and EBMI group was higher than that in RBMI group (P 0.05). The levels of Bax and Caspase-3 were higher than those of SH group (P 0.05), while the levels of Bax and Caspase-3 in EBMI group and RBMI group were lower than those in MI group (P 0.05), and EBMI group was lower than RBMI group (P 0.05). Conclusion: metoprolol succinate can reduce the degradation and dephosphorylation of gap junction protein, decrease the susceptibility to malignant arrhythmia and inhibit cardiomyocyte apoptosis by improving the spatial distribution of gap junction protein in ventricular muscle after myocardial infarction. It can protect the heart of myocardial infarction rabbits, and the benefit of early administration is more obvious.
【學(xué)位授予單位】：南方醫(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)】：R542.22

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