【摘要】： 目的：揭示UT-B基因缺失導致心肌肥大的分子機制,從而為疾病的防治提供理論依據(jù)和新思路。 方法：(1)UT-B基因缺失小鼠的飼養(yǎng)；(2)逆轉(zhuǎn)錄PCR鑒定UT-B基因敲除小鼠；(3) Realtime PCR鑒定mRNA表達變化請況；(4)乳鼠心肌細胞原代培養(yǎng)；(5)心臟組織尿素濃度測定；(6)免疫染色和組織學分析；(7)超聲心動圖分析；(8)血液動力學測定；(9)雙向電泳分析；(10)質(zhì)譜分析；(11)Western blot;(12)統(tǒng)計學分析。 結(jié)果：(1)UT-B基因敲除導致的尿素在心臟組織中的蓄積；(2)UT-B基因敲除導致心臟功能受損；(3)UT-B基因敲除導致的心肌肥厚和心肌纖維化；(4)ANP、TNNT2在UT-B基因敲除小鼠中動態(tài)表達；(5)Ras、Rafl、c-myc基因在UT-B基因敲除的小鼠中信號轉(zhuǎn)到通路中有明顯改變。 結(jié)論：(1)UT-B基因敲除導致的小鼠心臟功能障礙及心肌肥厚是一個隨年齡變化而加重的過程；(2)UT-B基因敲除導致小鼠心臟傳導阻滯使小鼠心臟中蛋白表達的改變是一個動態(tài)變化的過程；(3)UT-B基因敲除小鼠導致的小鼠心臟疾病使Ras-Raf信號傳導通路發(fā)生改變,使癌基因c-myc表達增高。
[Abstract]:Objective: to reveal the molecular mechanism of myocardial hypertrophy caused by UT-B gene deletion, so as to provide theoretical basis and new ideas for the prevention and treatment of diseases. Methods: (1) UT-B gene deletion mice were fed; (2) UT-B knockout mice were identified by reverse transcription PCR; (3) mRNA expression was detected by) Realtime PCR; (4) primary culture of neonatal rat cardiomyocytes; (5) determination of urea concentration in heart tissue; (6) immunostaining and histological analysis; (7) echocardiographic analysis; (8) hemodynamic determination; (9) two-dimensional electrophoresis analysis; (10) mass spectrometry analysis; (11) Western blot; (12) statistical analysis. Results: (1) the accumulation of urea in heart tissue caused by UT-B gene knockout, (2) the damage of cardiac function caused by UT-B gene knockout, (3) myocardial hypertrophy and myocardial fibrosis caused by UT-B gene knockout, and (3) myocardial hypertrophy and myocardial fibrosis caused by UT-B gene knockout. (4) ANP,TNNT2 was dynamically expressed in UT-B knockout mice, and (5) Ras,Rafl,c-myc gene was significantly changed in UT-B knockout mice. Conclusion: (1) the cardiac dysfunction and myocardial hypertrophy induced by UT-B gene knockout in mice are aggravated with the change of age. (2) the change of protein expression in mouse heart caused by cardiac block induced by UT-B gene knockout is a dynamic process. (3) the heart disease caused by UT-B knockout mice changed the Ras-Raf signal transduction pathway and increased the expression of c-myc.
【學位授予單位】：吉林大學
【學位級別】：博士
【學位授予年份】：2010
【分類號】：R363

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本文編號：2475462