本文選題：APOA4 + 肝臟��； 參考：《東北師范大學》2017年碩士論文

【摘要】：APOA4是一種血漿脂蛋白,參與許多代謝途徑,如脂質(zhì)代謝和葡萄糖代謝。APOA4最初由肝臟和小腸合成,隨后分泌到血液中。APOA4可以增強胰島素分泌并抑制肝臟中的葡萄糖產(chǎn)生,也可以增加肝臟中TG分泌。此外APOA4還具有抗氧化和抗炎的性質(zhì)。APOA4與一些疾病的關(guān)系也逐漸被發(fā)現(xiàn),如血漿中APOA4與可以抗動脈粥樣硬化形成。作為APOA4的合成器官之一,肝臟在VLDL合成分泌、脂質(zhì)代謝和葡萄糖代謝中有著重要作用。而肝臟也容易受到藥物和CCl4等化學毒物的損傷。但目前有關(guān)肝臟中APOA4是否調(diào)控動脈粥樣硬化與肝損傷在很大程度上還是未知的。因此,在本研究中,我們通過使用多種方法來確定肝臟中APOA4是否調(diào)控動脈粥樣硬化,以及其與肝損傷的聯(lián)系。最終獲得如下成果:第一:為研究肝臟中APOA4是否調(diào)控動脈粥樣硬化,我們通過雜交與基因型鑒定獲得了ob/ob APOE-/-雙基因敲除小鼠。并通過HFD飼喂法,獲得了HFD誘導ob/ob APOE-/-雙基因敲除動脈粥樣硬化小鼠模型,與常用單基因敲除小鼠相比,其形成動脈粥樣硬化所需時間明顯縮短,并伴有血脂和體重異常。第二:通過檢測HFD誘導ob/ob APOE-/-雙基因敲除動脈粥樣硬化小鼠模型,我們發(fā)現(xiàn)小鼠肝臟中APOA4水平異常升高。這一結(jié)果提示二者可能存在聯(lián)系,因此我們對模型小鼠肝臟中APOA4進行特異性敲低,檢測小鼠血脂水平與體重,觀察動脈粥樣硬化形成情況。結(jié)果表明,肝臟中APOA4可調(diào)節(jié)血漿TG水平,但對動脈粥樣硬化形成無顯著影響。第三:為了初步探討肝臟中APOA4與肝損傷是否存在聯(lián)系,我們建立了CCl4誘導的急性肝損傷小鼠模型,并發(fā)現(xiàn)CCl4誘導的急性肝損傷可引起小鼠肝臟中APOA4水平異常升高。結(jié)果提示肝臟中APOA4異常升高可能參與了CCl4誘導的肝臟損傷過程。綜上所述,本研究建立了HFD誘導ob/ob APOE-/-雙基因敲除動脈粥樣硬化小鼠模型。特異性敲低肝臟中APOA4可降低血漿TG水平,但對動脈粥樣硬化形成無顯著影響。同時肝損傷可引起肝損傷小鼠肝臟中APOA4水平異常升高,這提示APOA4可能調(diào)節(jié)了肝損傷。
[Abstract]:APOA4 is a plasma lipoprotein involved in many metabolic pathways, such as lipid metabolism and glucose metabolism. APOA4 is initially synthesized by the liver and small intestine and then secreted into the blood. APOA4 enhances insulin secretion and inhibits glucose production in the liver. It can also increase the secretion of TG in the liver. In addition, APOA4 has antioxidant and anti-inflammatory properties. APOA4 has been gradually found to be associated with some diseases, such as APOA4 in plasma and anti-atherosclerosis. As one of the synthetic organs of APOA4, liver plays an important role in VLDL synthesis and secretion, lipid metabolism and glucose metabolism. The liver is also vulnerable to drugs and CCL 4 and other chemical poisons. However, whether APOA4 regulates atherosclerosis and liver injury is still unknown. Therefore, in this study, we used a variety of methods to determine whether APOA4 in the liver regulates atherosclerosis and its association with liver injury. The results are as follows: first, in order to study whether APOA4 regulates atherosclerosis in liver, we obtained ob/ob APOE-r-double gene knockout mice by hybridization and genotyping. The model of ob/ob APOE-r-double gene knockout mice induced by HFD was obtained. Compared with the common single-gene knockout mice, the time required to form atherosclerosis was significantly shortened, and the blood lipid and body weight were abnormal. Second, we found that the level of APOA4 in the liver of ob/ob mice was abnormally elevated by detecting the mouse model of ob/ob APOE-r-double gene knockout induced by HFD-induced atherosclerosis. The results suggested that there might be a relationship between the two, so we specifically knock down APOA4 in the liver of model mice, detect the level of blood lipid and body weight, and observe the formation of atherosclerosis. The results showed that APOA4 could regulate plasma TG level, but had no significant effect on atherosclerosis. Third, in order to explore the relationship between APOA4 in liver and liver injury, we established a model of acute liver injury induced by CCl4, and found that acute liver injury induced by CCl4 could cause abnormal increase of APOA4 level in liver of mice. The results suggest that the abnormal increase of APOA4 may be involved in CCL 4 induced liver injury. To sum up, a HFD-induced ob/ob APOE-P-double knockout atherosclerosis model was established in this study. APOA4 could decrease plasma TG level, but had no significant effect on atherosclerosis. At the same time, liver injury can cause abnormal increase of APOA4 level in liver of mice, which suggests that APOA4 may regulate liver injury.
【學位授予單位】：東北師范大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R575

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