本文選題：心肌肥大 + 心肌營養(yǎng)素-1�。� 參考：《大連醫(yī)科大學(xué)》2006年碩士論文

【摘要】： 目的:在長期心臟負荷過重時,心肌細胞對增加的機械應(yīng)力和神經(jīng)體液因子采取一系列的代償適應(yīng)性肥大反應(yīng),表現(xiàn)為心肌細胞的形態(tài)改變和特征性的基因表達變化。因此,對心肌細胞肥大的細胞和分子水平改變的充分了解是治療心肌肥大及其隨后發(fā)生的心力衰竭的迫切要求。研究表明,心肌轉(zhuǎn)錄因子,尤其是鋅指結(jié)構(gòu)轉(zhuǎn)錄因子GATA-4,因其支持著正常情況下及肥大反應(yīng)后增加的各種結(jié)構(gòu)蛋白和收縮蛋白的轉(zhuǎn)錄調(diào)節(jié),而在多種肥大促進因素引起的心肌肥大反應(yīng)中發(fā)揮著關(guān)鍵性作用。 然而,GATA-4在一種新型的白細胞介素-6家族細胞因子成員——心肌營養(yǎng)素-1(Cardiotrophin-1, CT-1)引起心肌肥大過程中的作用尚未引起研究者的充分關(guān)注。CT-1是一種比目前已知的其他肥大激動劑更為強效的肥大促進因子,且CT-1所致的心肌肥大與G蛋白偶聯(lián)受體激動劑引起的肥大表型有所不同,更類似于容量負荷過重條件下的離心性肥大,且更易于轉(zhuǎn)變?yōu)椴豢赡娴男墓δ軗p害及心衰。本實驗的主要目的即為探討CT-1是否對GATA-4的轉(zhuǎn)錄及DNA結(jié)合活性產(chǎn)生影響。 方法:本實驗研究了10-12mol/L、10-11mol/L、10-10mol/L、10-9mol/L或10-8mol/L CT-1作用10分鐘、15分鐘、30分鐘、1小時、2小時、3小時、6小時、12小時、24小時或48小時后,對培養(yǎng)的新生大鼠心肌細胞內(nèi)GATA-4基因轉(zhuǎn)錄和DNA結(jié)合活性的影響;觀察了指示心肌肥大遺傳表型改變的ANP mRNA表達水平變化和CT-1作用下心肌細胞的形態(tài)學(xué)改變;同時還記錄了GATA-4的協(xié)同作用心肌轉(zhuǎn)錄因子Csx/Nkx2-5和MEF2C在CT-1刺激后的基因轉(zhuǎn)錄情況。 結(jié)果:為驗證實驗過程的有效性,本實驗首先觀察了CT-1對ANP基因轉(zhuǎn)錄的影響。ANP mRNA表達在對照組里幾乎檢測不到。10-10mol/L CT-1刺激后3小時開始引起ANP基因轉(zhuǎn)錄增加,且其表達
[Abstract]:Aim: during long-term cardiac overload, cardiomyocytes responded to increased mechanical stress and neurohumoral factors by a series of compensatory adaptive hypertrophy responses, which were characterized by morphologic changes and characteristic gene expression changes in cardiomyocytes. Therefore, a full understanding of the cellular and molecular changes of cardiac hypertrophy is an urgent requirement for the treatment of cardiac hypertrophy and its subsequent heart failure. Studies have shown that myocardial transcription factors, especially zinc finger structural transcription factor GATA-4, support the transcriptional regulation of various structural and contractile proteins in normal and hypertrophic response. It plays a key role in cardiac hypertrophy response caused by various hypertrophic factors. However, the role of GATA-4 in cardiac hypertrophy induced by cardiotrophin-1 (CT-1), a novel cytokine member of the interleukin-6 family, has not yet attracted sufficient attention from researchers. CT-1 is a type of hypertrophy compared with other known hypertrophy. Agonists are more potent hypertrophy promoters, The hypertrophy induced by CT-1 is different from that induced by G protein coupled receptor agonists, which is more similar to centrifugal hypertrophy under excessive volume loading, and it is more likely to change to irreversible cardiac dysfunction and heart failure. The main purpose of this study was to investigate whether CT-1 affects the transcription and DNA binding activity of GATA-4. Methods: the effects of 10-12 mol / L 10-11 mol / L 10 -10 mol / L 10 -9 mol / L or 10-8mol/L CT-1 on GATA-4 gene transcription and DNA binding activity in cultured neonatal rat cardiomyocytes were studied after exposure to 10-12 mol / L 10 -10 mol / L or 10-8mol/L CT-1 for 10 minutes, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 12 hours, 24 hours or 48 hours, respectively. The changes of ANP mRNA expression and morphologic changes of cardiomyocytes induced by CT-1 were observed, and the gene transcription of Csx/Nkx2-5 and MEF2C induced by CT-1 were also recorded. Results: to verify the effectiveness of the experimental process, we first observed the effect of CT-1 on ANP gene transcription. ANP mRNA expression was hardly detected in the control group. 10-10 mol / L CT-1 stimulated the ANP gene transcription increased 3 hours later, and its expression began to increase.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2006
【分類號】：R363

【共引文獻】

相關(guān)期刊論文 前10條

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2 金豐;李隆貴;耿召華;鄭宏庭;;大鼠壓力超負荷心肌糖蛋白130表達及貝那普利干預(yù)研究[J];第三軍醫(yī)大學(xué)學(xué)報;2006年20期

3 王寒明;高杰;章新華;王懷良;;氟西汀抑制野百合堿誘導(dǎo)的大鼠右心室肥厚及GATA結(jié)合蛋白4的表達[J];解剖科學(xué)進展;2010年01期

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7 姜升陽;徐明;張幼怡;;GATA結(jié)合蛋白4在心臟發(fā)育及心肌重塑中的作用[J];生理科學(xué)進展;2008年04期

8 劉澤廣;潘珊珊;郝U，

本文編號：1830895