本文選題：DIO大鼠 + 脂代謝��； 參考：《北京協(xié)和醫(yī)學(xué)院》2010年碩士論文

【摘要】：飲食誘導(dǎo)的肥胖(Diet-induced obesity, DIO)動(dòng)物模型能夠較好地模擬人類(lèi)肥胖的發(fā)病過(guò)程,但是DIO動(dòng)物的發(fā)病機(jī)制尚未完全闡明。本研究采用雄性SD大鼠作為模型動(dòng)物,通過(guò)飼喂高脂飼料成功誘導(dǎo)普通SD大鼠成為DIO大鼠,并通過(guò)Real-time PCR技術(shù),研究了本模型大鼠的發(fā)病機(jī)制。 結(jié)果表明,以脂肪含量為30%的高脂飼料飼喂25周,可以誘導(dǎo)普通SD大鼠成為DIO大鼠,造模成功率為45%。高脂飼料飼喂25周后,DIO組大鼠體重、Lee's指數(shù)和平均體脂總重量均顯著增加；肝臟脂肪異常蓄積,出現(xiàn)中重度脂肪肝；血清生化結(jié)果顯示,本DIO模型大鼠肝腎功能未見(jiàn)異常,血脂正常,空腹血糖及胰島素水平顯著升高,出現(xiàn)明顯的胰島素抵抗。 Real-time PCR的結(jié)果顯示,高脂飼料飼喂25周后,DIO組大鼠肝臟中脂肪酸合成的關(guān)鍵酶ACC和FAS表達(dá)量顯著增加,甘油三酯水解的限速酶HSL表達(dá)顯著增加；脂代謝相關(guān)酶的轉(zhuǎn)錄因子SREBP-1c表達(dá)水平達(dá)到正常組的2.56倍,兩組間差異極其顯著。 根據(jù)以上的研究結(jié)果,我們初步推測(cè)出DIO大鼠肥胖的發(fā)生與肝脂代謝相關(guān)基因及其轉(zhuǎn)錄調(diào)控的關(guān)系。長(zhǎng)期高脂飼料的飼喂使SD大鼠機(jī)體發(fā)生肥胖,脂肪組織的異常增加通過(guò)多種機(jī)制誘發(fā)機(jī)體產(chǎn)生胰島素抵抗,從而血清胰島素水平代償性增加。胰島素激活了肝臟中SREBP-1c的轉(zhuǎn)錄,SREBP-1c作為轉(zhuǎn)錄因子激活其靶基因ACC、FAS、HSL的表達(dá),從而使脂肪酸合成和甘油三酯水解增加,但是由于脂質(zhì)的合成速度大大超過(guò)分解速度,使脂代謝發(fā)生紊亂,導(dǎo)致脂肪在肝組織的異常蓄積,從而出現(xiàn)脂肪肝。由于SREBP-1c可抑制胰島素信號(hào)轉(zhuǎn)導(dǎo),使葡萄糖利用受阻,從而導(dǎo)致血糖逐漸升高。高血糖、胰島素抵抗、脂肪肝與肝脂代謝紊亂又進(jìn)一步加劇了肥胖的進(jìn)程。 綜上所述,本研究用高脂飼料飼喂SD大鼠25周,成功制作了伴有中重度脂肪肝、高血糖和胰島素抵抗的DIO大鼠模型,并通過(guò)檢測(cè)脂代謝相關(guān)基因的表達(dá)水平,初步闡釋了營(yíng)養(yǎng)性肥胖的發(fā)生與脂代謝變化之間的關(guān)系,為深入研究營(yíng)養(yǎng)性肥胖的發(fā)病機(jī)制奠定了基礎(chǔ)。
[Abstract]:Diet-induced obesity (dio) animal model can well simulate the pathogenesis of human obesity, but the pathogenesis of DIO animals has not been fully elucidated. In this study, male SD rats were used as model animals. The normal SD rats were induced to become DIO rats by feeding high fat diet. The pathogenesis of the model rats was studied by Real-time PCR technique. The results showed that the normal SD rats could be induced into DIO rats after 25 weeks of feeding with 30% high fat diet. The success rate of modeling was 45.5%. After 25 weeks of feeding with high fat diet, the body weight index and average body fat total weight of rats in DIO group were significantly increased, liver fat abnormal accumulation, moderate and severe fatty liver appeared, serum biochemical results showed that there was no abnormal liver and kidney function in this DIO model rats. With normal blood lipids, fasting blood glucose and insulin levels were significantly increased and insulin resistance was observed. The results of Real-time PCR showed that the expression of ACC and FAS, the rate-limiting enzyme HSL of triglyceride hydrolysis, was significantly increased in livers of rats fed with high-fat diet for 25 weeks. The expression level of transcription factor SREBP-1c was 2.56 times higher than that of the normal group, and the difference between the two groups was very significant. Based on the above results, we preliminarily speculated the relationship between obesity and liver lipid metabolism related genes and their transcriptional regulation in DIO rats. Long-term high-fat diet could induce obesity in SD rats, and the abnormal increase of adipose tissue could induce insulin resistance through various mechanisms, thus the level of serum insulin was compensatory. Insulin activates the expression of the target gene of SREBP-1c, SREBP-1c, as a transcription factor in the liver, thus increasing fatty acid synthesis and triglyceride hydrolysis, but the rate of lipid synthesis is much faster than that of decomposition. Disorder of lipid metabolism, leading to abnormal accumulation of fat in liver tissue, thus fatty liver. Because SREBP-1c can inhibit insulin signal transduction, glucose utilization is blocked, which leads to blood glucose increasing gradually. Hyperglycemia, insulin resistance, fatty liver and liver lipid metabolism disorders further exacerbate the process of obesity. To sum up, the DIO rat model with moderate and severe fatty liver, hyperglycemia and insulin resistance was successfully made by feeding SD rats with high fat diet for 25 weeks, and the expression level of genes related to lipid metabolism was detected. The relationship between the occurrence of nutritional obesity and the changes of lipid metabolism was preliminarily explained, which laid a foundation for the further study of the pathogenesis of nutritional obesity.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2010
【分類(lèi)號(hào)】：R589.2;R-332

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本文編號(hào)：1855903