發(fā)布時(shí)間：2018-02-20 00:03

  本文關(guān)鍵詞： 壓力超負(fù)荷 心肌肥厚 心肌細(xì)胞自噬 時(shí)程變化　出處：《山西醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:心肌細(xì)胞自噬在維持正常心臟結(jié)構(gòu)和功能中起重要作用。我們和其他前期研究表明,在小鼠壓力超負(fù)荷誘導(dǎo)心肌肥厚和心力衰竭模型上,在心力衰竭期,心肌細(xì)自噬明顯增加,增加的心肌細(xì)胞自噬與心肌細(xì)胞凋亡和心功能降低有關(guān)。然而,在壓力超負(fù)荷誘導(dǎo)心肌肥厚早期,心肌細(xì)胞自噬的變化尚未完全闡明。本研究在腹主動(dòng)脈縮窄誘導(dǎo)壓力超負(fù)荷大鼠模型上探究心肌細(xì)胞自噬的時(shí)程變化及其與心肌肥厚的關(guān)系。方法:1.動(dòng)物實(shí)驗(yàn)造模:體重180-200g雄性SD大鼠行腹主動(dòng)脈縮窄術(shù)(Abdominal aorta constriction,AAC),并設(shè)立假手術(shù)sham組,造模成功后分別于術(shù)后1h,3h,6h,24h,48h,72h處死。2.實(shí)驗(yàn)分組:(1)AAC組30只,分別于術(shù)后1h,3h,6h,24h,48h,72h不同時(shí)間點(diǎn)處死5只;(2)假手術(shù)組(sham)10只,分別于術(shù)后6h,72h各處死5只。3.心肌肥厚和心肌細(xì)胞自噬指標(biāo)測(cè)定:心臟重量和體重比率(HW/BW,心臟重量指數(shù)),左心室重量和體重比率(LVW/BW,左心室重量指數(shù))用于評(píng)估心肌肥厚;HE染色觀察心肌細(xì)胞大小的改變;應(yīng)用Western blot技術(shù)檢測(cè)心肌組織自噬相關(guān)蛋白的表達(dá)。結(jié)果:AAC術(shù)后AAC 1h和3h時(shí),與假手術(shù)相比,心臟重量和左心室重量指數(shù)沒有明顯變化,AAC術(shù)后6h,HW/BW比率有輕度增加趨勢(shì)。AAC術(shù)后24h時(shí),HW/BW比率,LVW/BW比率有進(jìn)一步增加趨勢(shì),48h和72h時(shí)顯著增加。AAC組72h與假手術(shù)sham組相比有統(tǒng)計(jì)學(xué)意義。HE染色顯示72h AAC組心肌細(xì)胞直徑較Sham組增大,細(xì)胞排列雜亂;免疫印跡結(jié)果表明,與假手術(shù)組相比,AAC組,心肌細(xì)胞自噬指標(biāo)LC3II/I比率,Beclin1和Atg12蛋白表達(dá)顯著降低。結(jié)論:壓力超負(fù)荷早期大鼠心臟心肌細(xì)胞自噬進(jìn)行性降低,心肌細(xì)胞自噬降低與心肌肥厚有關(guān)。提示在壓力超負(fù)荷誘導(dǎo)心肌肥厚早期,應(yīng)用心肌細(xì)胞自噬誘導(dǎo)劑可能有益于心肌肥厚的預(yù)防和治療。
[Abstract]:Objective: myocardial autophagy plays an important role in maintaining normal cardiac structure and function. Myocardial fine autophagy was significantly increased, and increased myocardial autophagy was associated with myocardial cell apoptosis and decreased cardiac function. However, at the early stage of pressure overload induced myocardial hypertrophy, increased myocardial autophagy was associated with a decrease in cardiac apoptosis and cardiac function. The changes of cardiac myocyte autophagy have not been fully elucidated. In this study, we investigated the relationship between myocardial autophagy and myocardial hypertrophy in a rat model of pressure overload induced by abdominal aortic coarctation. Model: male Sprague-Dawley rats weighing 180-200g underwent abdominal aorta constriction or abdominal aorta constriction, and set up sham-operated sham group. After successful modeling, the rats were killed at 1 h, 3 h, 6 h, 24 h, 48 h and 72 h, respectively. The rats were divided into three groups: 30 rats in the control group, and 5 rats in the sham operation group were killed at different time points at different time points (1 h, 3 h, 6 h, 24 h, 48 h, 72 h)) sham operation group (10 rats) were divided into two groups: the sham operation group (n = 10), the sham operation group (n = 10), the sham operation group (n = 10). Myocardial hypertrophy and myocardial autophagy: heart weight / body weight ratio: HW / BWR, left ventricular weight / body weight ratio LVW / BW, left ventricular mass / body weight ratio LVW / BW, left ventricular mass index (LVW / BW, left ventricular mass index). The changes of cardiac myocyte size were observed by HE staining. Western blot technique was used to detect the expression of autophagy related protein in myocardial tissue. Results compared with sham operation, the expression of autophagy related protein was detected at 1 h and 3 h after AAC. There was no significant change in cardiac weight and left ventricular mass index. There was a slight increase in HW / BW ratio at 6 h after AAC. There was a further increase in LVW / BW ratio at 24 h after AAC. There was a significant increase in LVW / BW ratio at 48 h and 72 h in AAC group as compared with sham operation sham group. He staining showed that the diameter of cardiomyocytes in AAC group was larger than that in Sham group at 72 h. The results of immunoblotting showed that the expression of LC3II/I ratio, Beclin1 and Atg12 protein in cardiomyocyte autophagy was significantly lower than that in sham-operated group. Conclusion: cardiac myocyte autophagy in rats at the early stage of pressure overload decreased progressively. The decrease of myocardial autophagy is related to myocardial hypertrophy, which suggests that the application of myocardial autophagy inducer may be beneficial to the prevention and treatment of myocardial hypertrophy at the early stage of pressure overload induced myocardial hypertrophy.
【學(xué)位授予單位】：山西醫(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)】：R542.2

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 趙美;臧偉進(jìn);;巨自噬在心臟疾病調(diào)節(jié)中的雙向作用[J];生理科學(xué)進(jìn)展;2011年02期

2 趙艷春;苗俊英;;血管內(nèi)皮細(xì)胞自噬的調(diào)節(jié)[J];生命的化學(xué);2009年06期

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本文編號(hào)：1518299