本文選題：高尿酸血癥模型 + 酵母　； 參考：《青島大學》2017年碩士論文

【摘要】：目的:隨著近年來高尿酸血癥患病率的持續(xù)升高,高尿酸血癥動物模型的建立更加引起了重視,但其造模方法尚未有統(tǒng)一定論,現(xiàn)有的動物模型仍然存在一定的問題。故本研究擬采用酵母和果糖聯(lián)合的新型造模方法誘導(dǎo)大鼠建立高尿酸血癥模型,觀察其對大鼠持續(xù)性高尿酸血癥形成的影響;通過對尿酸代謝途徑的研究,初步探討果糖聯(lián)合酵母維持大鼠高尿酸水平的機制。方法:選用雄性Wistar大鼠50只,按體質(zhì)量隨機分為五組,每組10只,分別為對照組、酵母組、果糖組、酵母氧嗪酸鉀組(高尿酸血癥傳統(tǒng)模型組)、酵母果糖組。對照組與果糖組給予普通大鼠顆粒飼料喂養(yǎng),其他三組給予質(zhì)量分數(shù)0.2酵母飼料喂養(yǎng);果糖組與酵母果糖組大鼠給予10%果糖飲水,其他三組給予自來水;酵母氧嗪酸鉀組予以500mg/(kg·d)氧嗪酸鉀灌胃。分別在第2、4、6、8周末剪尾取血,測定各組血清尿酸(SUA)、血清尿素氮(BUN)、血清肌酐(SCr)水平。在第8周末時,收集24h尿液,測定尿中尿酸(UUA)、肌酐(UCr),計算尿酸清除率(CUA)和肌酐清除率(CCR)。干預(yù)8周后,處死大鼠,檢測血清及肝勻漿中腺苷脫氨酶(ADA)和黃嘌呤氧化酶(XOD)活性,并觀察腎臟組織學病理切片。采用Western blotting檢測大鼠腎臟有機陰離子轉(zhuǎn)運子1(OAT1)、腎臟尿酸鹽轉(zhuǎn)運體(RST)、葡萄糖轉(zhuǎn)運蛋白9(GLUT9)的蛋白表達水平。結(jié)果:實驗第2、4、6、8周末,酵母果糖組大鼠血清SUA水平分別達到345.9μmol/L,403.7μmol/L,447.2μmol/L和451.4μmol/L;與對照組相比分別升高了66.5%、33.8%、37.5%和69.8%(P值均0.05);而酵母氧嗪酸鉀組(傳統(tǒng)模型組)大鼠SUA水平與對照組相比也顯著升高(P值均0.05),分別在實驗第2、4、6、8周末升高了28.8%、54.4%、39.4%和75.1%,顯示造模成功。在第2周末,酵母果糖組大鼠SUA水平與酵母組、果糖組、酵母氧嗪酸鉀組相比顯著升高(P值均0.05),分別升高了31.7%、52.9%、29.3%,顯示酵母果糖組SUA升高最快;在第8周末,酵母果糖組與酵母氧嗪酸鉀組大鼠SUA水平分別是對照組的2.24倍、2.17倍,顯示果糖具有氧嗪酸鉀類似的促進血清尿酸升高的作用。與嘌呤代謝相關(guān)的XOD和ADA活性分析顯示,酵母果糖組大鼠血清和肝勻漿中XOD活性分別達到46.3U/L和10.4U/L,明顯高于空白對照組(38.2U/L和7.7U/L,P值均0.05);而ADA活力也分別達到26.8U/L和15.3U/L,顯著高于對照組(19.5U/L和11.1U/L,P值均0.05)。與對照組相比,酵母果糖組大鼠24h尿量明顯增加,CUA明顯降低(P值均0.05)。腎臟病理組織學分析顯示,在第8周,酵母果糖組大鼠腎小管管腔間質(zhì)偶見結(jié)晶物沉積,無明顯纖維化,腎小管、腎小球組織結(jié)構(gòu)無明顯異常;酵母氧嗪酸鉀組大鼠腎臟偶見間質(zhì)片灶狀單核淋巴細胞浸潤,無明顯纖維化改變。Western blotting結(jié)果顯示,與對照組相比,酵母果糖組大鼠腎臟OAT1水平明顯下降,RST水平明顯升高(P值均0.05)。結(jié)論:果糖聯(lián)合酵母可快速誘發(fā)高尿酸血癥的出現(xiàn),引起腎臟炎癥反應(yīng)較小,穩(wěn)定性與持續(xù)性較好,可作為開展嘌呤代謝研究的良好模型;同時,提示攝入高嘌呤食物時應(yīng)避免果糖的過量攝入。
[Abstract]:Objective: with the increasing prevalence of hyperuricemia in recent years, the establishment of hyperuricemia animal model has become more and more important, but its modeling method has not yet been unified, the existing animal models still have some problems. Therefore, a new model method of combination of yeast and fructose is used to induce the establishment of high uric acid in rats. The effects of hyperuricemia on the formation of persistent hyperuricemia in rats were observed. Through the study of the metabolic pathway of uric acid, the mechanism of sustaining the high uric acid level of rats with fructose and yeast was preliminarily studied. Methods: 50 male Wistar rats were randomly divided into five groups according to the body mass, 10 in each group, which were the control group, the yeast group, the fructose group, and the fermentation. The control group and fructose group were fed with normal rat pellet feed and the other three groups were fed with 0.2 yeast feed, the fructose group and the yeast fructose group were given 10% fructose drinking water, the other three groups were given tap water, and the yeast oxazine potassium group was given 500mg/ (kg. D). The serum uric acid (SUA), serum urea nitrogen (BUN) and serum creatinine (SCr) levels were measured at the end of the 2,4,6,8 week, and the urine acid (UUA) and creatinine (UCr) in the urine were collected at the eighth weekend, and the urine acid removal rate (CUA) and creatinine clearance rate (CCR) were calculated. After 8 weeks, the rats were killed and the serum and liver were detected. The activity of adenosine deaminase (ADA) and xanthine oxidase (XOD) in the homogenate and the histological pathological sections of the kidney were observed. Western blotting was used to detect the organic anion transporter 1 (OAT1), renal urate transporter (RST) and glucose transporter 9 (GLUT9) protein expression level in rats. Results: experimental 2,4,6,8 weekend, yeast fructose group The serum SUA levels of rats were 345.9, 403.7, 447.2, and 451.4 mol/L, respectively, and increased by 66.5%, 33.8%, 37.5% and 69.8%, respectively, compared with the control group (P value was 0.05), while the SUA level of the yeast oxazine group (the traditional model group) was significantly higher than that of the control group (P value was 0.05), respectively, and increased at the end of the experiment at the end of the experiment. 28.8%, 54.4%, 39.4% and 75.1% were successful. At the end of the second week, the SUA level in the yeast fructose group was significantly higher than that in the yeast group, the fructose group and the yeast oxazine group (P value 0.05), which increased by 31.7%, 52.9%, 29.3% respectively, indicating that the yeast fructose group SUA increased the fastest; in eighth weekend, the yeast fructose group and the yeast oxazine potassium group rat SU The level of A was 2.24 times and 2.17 times that of the control group, which showed that fructose had a similar effect on the increase of serum uric acid. The activity of XOD and ADA related to purine metabolism showed that the activity of XOD in the serum and liver homogenate of the yeast fructose group was 46.3U/L and 10.4U/L respectively, which was significantly higher than that of the blank control group (38.2U/L and 7.7U/L, P value). The activity of ADA also reached 26.8U/L and 15.3U/L, which was significantly higher than that of the control group (19.5U/L and 11.1U/L, P value was 0.05). Compared with the control group, the 24h urine volume increased significantly in the yeast fructose group and the CUA decreased significantly (P value was 0.05). The renal histopathology analysis showed that in the eighth weeks, the renal tubule interstitium in the yeast fructose group was crystallized. There was no obvious fibrosis, renal tubules and glomerular structure without obvious abnormalities. The kidney of the group of yeast oxazine group showed interstitial mononuclear lymphocyte infiltration and no obvious fibrosis changes.Western blotting results showed that the OAT1 level of the kidney of the yeast fructose group decreased significantly and the RST level was significantly higher than that of the control group. (P value is 0.05). Conclusion: fructose combined yeast can quickly induce hyperuricemia, resulting in less renal inflammation and better stability and sustainability. It can be used as a good model for the study of purine metabolism. At the same time, it is suggested that the excessive intake of fructose should be avoided when eating high purine food.
【學位授予單位】：青島大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R589.7;R-332

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