本文關(guān)鍵詞：氧化應(yīng)激與內(nèi)質(zhì)網(wǎng)應(yīng)激在小鼠心肌功能中的研究　出處：《河北大學(xué)》2009年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 氧化應(yīng)激 內(nèi)質(zhì)網(wǎng)應(yīng)激 谷胱甘肽 心肌細(xì)胞 金屬硫蛋白

【摘要】：氧化應(yīng)激和內(nèi)質(zhì)網(wǎng)應(yīng)激已經(jīng)被牽涉到心臟病領(lǐng)域,盡管二者之間的關(guān)系仍然不很明確。本實(shí)驗(yàn)采用野生型Friend virus B (FVB)小鼠和金屬硫蛋白(MT)轉(zhuǎn)基因小鼠來(lái)研究谷胱甘肽缺失引起的氧化應(yīng)激對(duì)內(nèi)質(zhì)網(wǎng)應(yīng)激和心肌收縮功能的影響。FVB和MT轉(zhuǎn)基因小鼠分別用GSH合成酶抑制劑丁硫堇(Buthionine sulfoximine, BSO)食用水溶液(30mmol/L)喂養(yǎng)兩周。分別通過(guò)對(duì)GSH/GSSG、活性氧自由基(reactive oxygen species, ROS)、caspase-3活性的檢測(cè)以及蛋白免疫印記、Langendorff心臟離體灌流(LVDP和±dP／dt指標(biāo))以及電鏡技術(shù)來(lái)對(duì)氧化應(yīng)激、細(xì)胞凋亡、內(nèi)質(zhì)網(wǎng)應(yīng)激、心肌功能和心室超微結(jié)構(gòu)進(jìn)行評(píng)定。結(jié)果發(fā)現(xiàn)BSO顯著降低了GSH/GSSG比率,增加了ROS的產(chǎn)生,從而鞏固了氧化應(yīng)激。心肌功能和心室超微結(jié)構(gòu)在BSO處理后也發(fā)生了顯著的變化,而這些損傷明顯被MT所減輕。BSO通過(guò)上調(diào)BiP、calreguln、p-IRE1α和p-eIF2α蛋白的表達(dá)而觸發(fā)了內(nèi)質(zhì)網(wǎng)應(yīng)激,但是并沒(méi)有影響IRE1α和eIF2α總蛋白的表達(dá)量。同時(shí)BSO引起了CHOP/GADD153、caspase-12、Bax蛋白表達(dá)量的上調(diào)并增加了caspase-3的活性,減少了Bcl-2和p-JNK蛋白的表達(dá),從而引起細(xì)胞凋亡,而MT明顯改善了細(xì)胞凋亡的程度。另外,抗氧化劑N-乙酰半胱氨酸(N-acetylcysteine, NAC)和內(nèi)質(zhì)網(wǎng)應(yīng)激抑制劑牛熊去氧膽酸(tauroursodeoxycholic acid, TUDCA)明顯扭轉(zhuǎn)了氧化應(yīng)激誘導(dǎo)劑甲萘醌(menadione)引起的心肌收縮功能降低的趨勢(shì)。綜上所述,所有這些數(shù)據(jù)表明內(nèi)質(zhì)網(wǎng)應(yīng)激在引發(fā)心肌功能損傷中可能位于氧化應(yīng)激下游起作用。
[Abstract]:Oxidative stress and endoplasmic reticulum stress have been implicated in cardiovascular diseases, although the relationship between the two is not clear. In this experiment, the wild type Friend virus B (FVB) mice and metallothionein (MT) oxidative stress in mice transgenic mice to study the effect of glutathione depletion of endoplasmic reticulum stress and myocardial contraction the function of.FVB and MT respectively with GSH synthase inhibitor buthionine sulfoximine (Buthionine sulfoximine, BSO) in drinking water (30mmol/L) for two weeks respectively. Based on GSH/GSSG, active oxygen free radicals (reactive oxygen, species, ROS), to detect the activity of Caspase-3 and Western blot, Langendorff isolated heart perfusion (LVDP and + dP / dt index) and electron microscopy of oxidative stress, apoptosis, endoplasmic reticulum stress, myocardial function and ventricular ultrastructure were evaluated. The results show that BSO significantly reduced GSH/GSSG The ratio increased ROS production, thereby consolidating oxidative stress. Myocardial function and ventricular ultrastructure also changed significantly after BSO treatment, and the obvious injury by MT reduce.BSO through upregulation of BiP, calreguln, p-IRE1 and p-eIF2 expression of alpha alpha protein triggered endoplasmic reticulum stress, but did not the expression of IRE1 and alpha eIF2 alpha total protein amount. At the same time, caused by BSO CHOP/GADD153, caspase-12, Bax protein expression was up-regulated and increased the activity of Caspase-3, reduce the expression of Bcl-2 and p-JNK proteins, which induce cell apoptosis, and MT significantly improved the extent of apoptosis. In addition, the antioxidant N-acetylcysteine (N- N-acetylcysteine, NAC) and endoplasmic reticulum stress inhibitor tauroursodeoxycholic acid (tauroursodeoxycholic acid, TUDCA) significantly reversed the oxidative stress inducer (menadione) induced by myocardial systolic function A downward trend. In summary, all of these data suggest that endoplasmic reticulum stress may play a role in the cause of myocardial dysfunction that may be downstream of oxidative stress.

【學(xué)位授予單位】：河北大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2009
【分類號(hào)】：R363

【引證文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前2條

1 韓佳;結(jié)香花化學(xué)成分的提取分離及其抑菌、抗氧化活性研究[D];西南交通大學(xué);2011年

2 趙猛;HO-1高表達(dá)對(duì)2型糖尿病大鼠心肌氧化應(yīng)激與內(nèi)質(zhì)網(wǎng)應(yīng)激的影響[D];遼寧醫(yī)學(xué)院;2012年

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本文編號(hào)：1379651