本文選題：高尿酸 + 學(xué)習(xí)記憶��； 參考：《四川醫(yī)科大學(xué)》2015年碩士論文

【摘要】：目的:觀察高尿酸血癥(hyperuricemia,HUA)對(duì)成年大鼠認(rèn)知功能(cognitive function)的影響,探究HUA影響認(rèn)知功能的具體機(jī)制。方法:健康、成年(8周齡)雄性SD大鼠75只,體重200±20 g。隨機(jī)分為三組:空白對(duì)照組,蒸餾水組,高尿酸組,25只/組。采用酵母膏聯(lián)合乙胺丁醇(尿酸酶抑制劑)灌胃法建立高尿酸血癥動(dòng)物模型,空白組不做任何處理,蒸餾水組灌胃與高尿酸組等量的蒸餾水。每天選取固定時(shí)間點(diǎn)進(jìn)行灌胃操作,每周末選取固定時(shí)間點(diǎn)取眼球血測(cè)定各組大鼠血尿酸濃度。第7周末,應(yīng)用Morris水迷宮實(shí)驗(yàn)檢測(cè)大鼠學(xué)習(xí)記憶能力(逃避潛伏期、跨越原平臺(tái)次數(shù))(17只/組),然后隨機(jī)選取大鼠9只/組,分離其海馬組織進(jìn)行勻漿,取上清液測(cè)定海馬組織中丙二醛(MDA),谷胱甘肽過氧化物酶(GSH-Px),抗超氧陰離子(ASAFR)及過氧化物歧化酶(SOD)活力等氧化應(yīng)激指標(biāo),將剩余大鼠海馬組織(8只/組)進(jìn)行HE染色,光鏡下觀察海馬區(qū)神經(jīng)元細(xì)胞形態(tài)學(xué)結(jié)構(gòu),TUNEL法(細(xì)胞凋亡末端標(biāo)記法)觀察海馬區(qū)錐形細(xì)胞凋亡情況,計(jì)數(shù)凋亡指數(shù)(AI%)。結(jié)果:1.高尿酸模型:第三周末高尿酸組大鼠的尿酸水平已經(jīng)達(dá)到285μmol/L,以后一直保持高尿酸水平,表明已經(jīng)造模成功;2.Morris水迷宮實(shí)驗(yàn):1)隨著訓(xùn)練時(shí)間的延長,各組大鼠定位航行實(shí)驗(yàn)時(shí)間縮短;在同一時(shí)間段,與空白組和蒸餾水組比較,高尿酸組大鼠尋找平臺(tái)的平均逃避潛伏期無明顯縮短(P0.05);2)與空白組和蒸餾水組相比,高尿酸組空間探索實(shí)驗(yàn)穿越平臺(tái)次數(shù)明顯增多,但差異無統(tǒng)計(jì)學(xué)意義(P0.05);3.氧化應(yīng)激指標(biāo):與空白組和蒸餾水組相比,高尿酸組大鼠海馬組織中MDA含量明顯降低(P0.05);GSH-Px,ASAFR,SOD含量明顯增高(P0.05);4.病理學(xué)變化:HE染色后光鏡下觀察空白組、蒸餾水組及高尿酸組大鼠海馬神經(jīng)元細(xì)胞形態(tài)、大小基本正常,呈圓形、橢圓形狀,排列緊密,錐形細(xì)胞數(shù)目無明顯減少,細(xì)胞核淡藍(lán)色染色,著色較均勻,核仁清晰可見,核膜完整。未見細(xì)胞水腫,無明顯核固縮及核碎裂等病變細(xì)胞,三組比較無明顯差異。TUNEL細(xì)胞凋亡檢測(cè)法顯示,各組大鼠海馬區(qū)未見明顯錐形細(xì)胞凋亡,相比空白組和蒸餾水組,高尿酸組凋亡指數(shù)(AI%)亦無明顯減少(P0.05)。結(jié)論:1.通過酵母膏聯(lián)合乙胺丁醇灌胃法制作高尿酸血癥大鼠模型,操作簡單可行,與人體形成高尿酸血癥的病理生理過程極為相似,是目前研究高尿酸血癥及其相關(guān)疾病較為穩(wěn)定且理想的動(dòng)物模型;2.5W高尿酸水平未見對(duì)實(shí)驗(yàn)大鼠學(xué)習(xí)記憶能力有明顯影響;3.罹患5W高尿酸血癥能有效減少有害氧化應(yīng)激自由基的產(chǎn)生,增加自由基清除率,減輕氧化應(yīng)激反應(yīng)帶來的損傷;4.5W高尿酸水平未見大鼠海馬區(qū)神經(jīng)元細(xì)胞明顯病理學(xué)改變。
[Abstract]:Aim: to observe the effect of hyperuricemia on cognitive function in adult rats and to explore the mechanism of HUA affecting cognitive function.Methods: 75 male Sprague-Dawley rats (body weight 200 鹵20 g) were healthy and 8 weeks old.They were randomly divided into three groups: blank control group, distilled water group and high uric acid group.The animal model of hyperuricemia was established by yeast extract combined with ethambutanol (uric acid inhibitor). The blank group was not treated, and the distilled water group was given the same amount of distilled water as the high uric acid group.Fixed time points were selected for gastric perfusion and eyeball blood samples were taken to determine the concentration of uric acid in each group.At the end of the 7th week, Morris water maze test was used to detect the ability of learning and memory (escape latency, number of times across the original platform) in 17 rats / group, and then 9 rats were randomly selected for homogenization of hippocampal tissue.The activity of malondialdehyde (MDA), glutathione peroxidase (GSH-PxX), anti-superoxide anion (ASAFR) and superoxide dismutase (SOD) in hippocampus were determined by HE staining.The morphological structure of hippocampal neurons was observed under light microscope. The apoptosis of conical cells in hippocampal area was observed by Tunel method and the apoptotic index was counted.The result is 1: 1.Model of hyperuricemia: at the end of the third week, the uric acid level of the rats in the high uric acid group reached 285 渭 mol / L, and maintained high uric acid level since then, indicating that the model had been successfully made and Morris water maze experiment: 1) with the prolongation of training time,In the high uric acid group, the frequency of space exploration through the platform increased obviously, but the difference was not statistically significant (P 0.05).Index of oxidative stress: compared with blank group and distilled water group, the content of MDA in hippocampus of rats in high uric acid group was significantly lower than that in control group and distilled water group.The pathological changes were observed under light microscope in the blank group, distilled water group and high uric acid group. The hippocampal neurons were normal in size, round in shape, elliptical in shape, compact in arrangement, and no significant decrease in the number of conical cells.The nuclei were stained with light blue with uniform staining, clear nucleolus and intact nuclear membrane.No cell edema, nuclear pyknosis, nuclear fragmentation and other pathological cells were found in the three groups. Tunel cell apoptosis assay showed that there was no obvious cone cell apoptosis in the hippocampus of rats in each group, compared with the blank group and distilled water group.The apoptotic index (AI) in high uric acid group was not significantly decreased (P 0.05).Conclusion 1.The rat model of hyperuricemia was made by yeast extract combined with ethambutanol. The operation was simple and feasible, which was very similar to the pathophysiological process of the formation of hyperuricemia in human body.It is a stable and ideal animal model to study hyperuricemia and its related diseases at present. There is no significant effect on learning and memory ability of experimental rats by 2.5 W hyperuricemia.5 W hyperuricemia could effectively reduce the production of harmful oxidative stress free radicals, increase the free radical clearance rate, and alleviate the damage caused by oxidative stress reaction. There were no obvious pathological changes of neurons in the hippocampal area of rats with hyperuricemia at 4.5 W.
【學(xué)位授予單位】：四川醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R589.7

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