本文選題：非酒精性脂肪肝病 + 肝功能　； 參考：《山東大學》2017年碩士論文

【摘要】：[背景/目的]非酒精性脂肪肝病(nonalcoholic fatty liver disease,NAFLD)是常見以脂質堆積、酶學指標持續(xù)異常為特點的臨床病理表現(xiàn),是慢性肝臟疾病中的一個常見原因,是世界上一個重大的問題。調查結果顯示,肥胖促進NAFLD病情加重。免疫球蛋白E(IgE)是介導I型變態(tài)反應的一種免疫球蛋白,高親和力IgE受體(FcεRl)是IgE的受體之一。Yun-Jung Lee等人做了一項研究,檢測隨機抽取的50名肥胖婦女的血漿IgE,體質量和體重指數(shù)(BMI),粗略估計脂肪的含量,對此數(shù)據(jù)進行分析,發(fā)現(xiàn)血漿IgE水平隨其他三項指標的升高而降低。并且做了相關動物實驗,發(fā)現(xiàn)高脂飲食(HFD)誘導的FcεR1-/-肥胖小鼠進食量增加和能量代謝降低,導致體質量增加。本研究旨在通過HFD誘導小鼠NAFLD模型,探討FcdR1在NAFLD發(fā)生發(fā)展中的作用。[方法]1.NAFLD模型的建立及指標檢測:隨機選取野生型C57BL/6J和IgE受體敲除FcεR1R/-、鼠各10只,分為野生型組(WT)和基因敲除組(FcεR1R-/-),均給予HFD喂養(yǎng),在每周一定的時間稱取其體質量。喂養(yǎng)12周后,小鼠禁食12h,稱取體質量后處死取材。取全血,離心后取血漿,用生化檢測儀檢測血漿中谷丙轉氨酶(ALT)、谷草轉氨酶(AST)、甘油三酯(TG)、總膽固醇(TC)等指標。馬上快速剪斷肝血管并取出肝臟,稱取重量后分別制成組織石蠟切片和冰凍切片,分別用于HE、masson和油紅O染色,剩余部分置于-80℃C擱置,用于檢測肝組織中TG、Ⅰ型膠原(collagenⅠ)和Ⅲ型膠原(collagenⅢ)等指標。2.胰島素耐受實驗(ITT):HFD喂養(yǎng)小鼠第10周時,禁食6h,腹部打入胰島素(0.66IU/kg),打的同時開始計時,分別于0、30、60、90、120、150min用血糖針扎尾取血,用血糖儀檢測血糖值,根據(jù)系列數(shù)據(jù)作ITT曲線,觀察小鼠對胰島素的耐受情況。3.葡萄糖耐受實驗(GTT):HFD喂養(yǎng)小鼠第11周時,禁食12h,腹部打入葡萄糖(2g/kg),打的同時開始計時,分別于0、30、60、90、120、150min用血糖針扎尾取血,檢測血糖值,根據(jù)系列數(shù)據(jù)作GTT曲線,觀察小鼠對葡萄糖的控制情況。[結果]1.體質量和肝臟體重比的比較結果:與WT小鼠相比,FcεR1-/-小鼠體質量增長速度和肝臟體重比均明顯增加。2.肝功能和肝組織纖維化的比較結果:與WT小鼠相比,FcεR1-/-、鼠血漿ALT和AST水平升高,肝組織collagenⅢ含量增加,collagenⅠ含量無明顯變化,肝組織HE染色提示小鼠肝細胞腫脹及空泡樣變較重,肝組織masson染色提示肝臟中纖維生成和堆積量增多,且陽性面積比增加。3.脂質代謝的比較結果:與WT小鼠相比,FcεR1-/-小鼠血漿TG和TC水平顯著升高,小鼠肝組織TG堆積量增加,油紅O染色提示肝臟脂質堆積程度較重,且陽性面積比增加。4.ITT和GTT的比較結果:WT和FcεR1-/-兩組小鼠的ITT和GTT實驗結果無明顯差異,但是均對胰島素敏感性下降,對葡萄糖控制較差。[結論]敲除FcεR1后,HFD誘導的NAFLD小鼠體質量升高,脂質代謝雜亂,NAFLD程度加重,而胰島素抵抗(IR)無明顯改變,提示FcεR1通過調節(jié)脂質代謝,不同程度的干預了小鼠NAFLD的進展,而此過程與IR無關。
[Abstract]:[background / purpose] nonalcoholic fatty liver disease (NAFLD) is a common clinical pathological manifestation characterized by lipid accumulation and persistent abnormalities of enzymology. It is a common cause of chronic liver disease. It is a major problem in the world. The results of investigation show that obesity promotes the aggravation of NAFLD, immune ball. Protein E (IgE) is an immunoglobulin which mediates I type allergy. The high affinity IgE receptor (Fc e Rl) is one of the IgE receptor.Yun-Jung Lee et al. A study was conducted to detect the plasma IgE, body mass and body mass index (BMI) of 50 randomly selected obese women. The content of fat was roughly estimated. The data were analyzed and plasma IgE was found. The level decreased with the increase of the other three indicators. And in the related animal experiments, we found that high fat diet (HFD) induced Fc epsilon R1-/- obese mice had increased food intake and reduced energy metabolism, resulting in increased body mass. The purpose of this study was to explore the role of FcdR1 in the development of NAFLD in mice by HFD induced NAFLD model. [method]1.NAFLD model]. Model establishment and index detection: random selection of wild type C57BL/6J and IgE receptor knockout Fc epsilon R1R/-, 10 rats each, divided into wild type group (WT) and gene knockout group (Fc epsilon R1R-/-), were given HFD feeding, and were given the body mass at the time fixed every Monday. After feeding 12 weeks, the mice were fasted 12h after being weighed. Take the whole blood, take the blood after centrifugation and take blood. Plasma, the serum ALT, AST, TG, and total cholesterol (TC) were detected by the biochemical analyzer. The liver vessels were quickly cut off and removed from the liver. After the weight, the tissue paraffin section and frozen section were made respectively, and respectively used for HE, Masson and oil red O staining, and the remaining part was placed in -80 and C shelved. TG, type I collagen (collagen I) and type III collagen (collagen III) were tested for.2. insulin tolerance test (ITT). After tenth weeks of HFD feeding mice, 6h was fasted, insulin (0.66IU/kg) was injected into the abdomen, and the timing was started at the same time. .3. glucose tolerance test (GTT) of mice's tolerance to insulin (GTT) was observed in a series of data. At eleventh weeks of HFD feeding mice, HFD was fed to 12h, the abdomen was injected into glucose (2g/kg), and the time was recorded at the same time. The blood glucose was measured by the tail of blood glucose needle in 0,30,60,90120150min, and the blood glucose was detected, and the GTT curve was observed according to the series of data. The mice were observed and observed. The control of glucose was compared with the results of]1. body mass and liver weight ratio: compared with WT mice, the growth rate of Fc epsilon R1-/- mice and the liver weight ratio significantly increased the results of.2. liver function and liver tissue fibrosis: compared with the WT mice, Fc e R1-/-, the increase of ALT and AST levels in the rat plasma, and the collagen III containing liver tissue There was no obvious change in the content of collagen I. The liver tissue HE staining showed that the liver cells were swelling and the vacuoles were heavier. Masson staining in the liver showed the increase of fibrous formation and accumulation in the liver, and the positive area was compared with the increase of.3. lipid metabolism: compared with the WT mice, the level of TG and TC in the plasma of Fc e R1-/- mice was significantly higher. The accumulation of TG in the rat liver was increased. The lipid accumulation in the liver was heavier with the oil red O staining, and the positive area was compared with the increase of.4.ITT and GTT. There was no significant difference between the ITT and GTT experimental results of WT and Fc epsilon two groups, but the sensitivity to insulin decreased and the control of grape sugar was poor. [Conclusion] after knocking Fc epsilon R1, HFD induction The body mass of LD mice increased, lipid metabolism was disorderly, the degree of NAFLD increased, and the insulin resistance (IR) had no obvious change. It suggested that Fc e R1 intervened the progress of NAFLD in mice by regulating lipid metabolism, and this process was not related to IR.
【學位授予單位】：山東大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R575.5

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1 崔杏杏;高親和力IgE受體FcεR1與非酒精性脂肪肝病關系的實驗研究[D];山東大學;2017年

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