本文選題：尿酸 + 動物模型�。� 參考：《川北醫(yī)學(xué)院》2017年碩士論文

【摘要】：目的:(1)了解不同高尿酸水平對大鼠血清抗氧化能力及腎臟損傷的影響,同時為創(chuàng)建一個穩(wěn)定的高尿酸動物模型提供幫助。(2)同時建立低尿酸模型,探討低尿酸水平對大鼠的影響。(3)探討一種最佳的尿酸控制范圍,為將來尿酸對臨床疾病的預(yù)防及治療提供一定依據(jù)。方法:(1)選取64只雄性SD大鼠隨機分成8組。(2)第一組(對照組)每天灌胃蒸餾水;第二組(低尿酸組)每天按照25mg/kg灌胃苯溴馬隆;第三組(高尿酸1組)每天按照20g/kg灌胃酵母膏+100mg/kg灌胃氧嗪酸鉀;第四組(高尿酸2組)每天按照20g/kg灌胃酵母膏+200mg/kg灌胃氧嗪酸鉀;第五組(高尿酸3組)每天按照20g/kg灌胃酵母膏+300mg/kg灌胃氧嗪酸鉀;第六組(高尿酸4組)每天按照20g/kg灌胃酵母膏+400mg/kg灌胃氧嗪酸鉀;第七組(高尿酸5組)每天按照20g/kg灌胃酵母膏+500mg/kg灌胃氧嗪酸鉀;第八組(高尿酸6組)每天按照20g/kg灌胃酵母膏+600mg/kg灌胃氧嗪酸鉀;以上藥物每日兩次灌胃完成,實驗期間大鼠每日稱重并根據(jù)體重調(diào)整給藥劑量。(3)每周經(jīng)內(nèi)眥靜脈采血一次,分離出血清進行尿酸(UA)、尿素氮(BUN)、肌酐(Cr)、超氧化物歧化酶(SOD)、谷胱甘肽過氧化物酶(GSH-PX)、丙二醛(MDA)檢測。(4)連續(xù)采血六周后處死大鼠,分離并切除腎臟,分別用于HE染色、masson特殊染色及電鏡觀察。結(jié)果:(1)各組間UA檢測:低尿酸組造模過程中UA較對照組明顯降低;所有高尿酸組UA水平均表現(xiàn)為于造模第二周達(dá)到高峰后稍下降并維持在較高水平,且UA升高程度與所給藥物成劑量依賴性。(2)各組間Cr檢測:造模過程中對照組、低尿酸組、高尿酸1組Cr未見明顯改變;高尿酸組(2-3組)第二周Cr較對照組輕微升高,于造模第三周基本恢復(fù)正常;高尿酸組(4-6組)于造模第一周Cr較對照組稍微升高,造模第二周達(dá)到高峰,于造模第四周基本降至對照組水平。(3)各組間BUN檢測:造模過程中對照組、低尿酸組BUN未見明顯異常;所有高尿酸組造模過程中BUN維持在較高水平。(4)各組間抗氧化能力檢測:造模過程中對照組未見明顯改變;造模過程中低尿酸組及高尿酸組(1-3組)血清SOD、GSH-PX較對照組升高、MDA較對照組稍低;而高尿酸組(4-6組)血清SOD、GSH-PX較對照組降低,MDA較對照組明顯升高。(5)腎臟病理觀察:低尿酸組及所有高尿酸組光鏡下均表現(xiàn)為腎小球及腎間質(zhì)充血、腎小管擴張、腎間質(zhì)炎細(xì)胞浸潤伴纖維化,電鏡下表現(xiàn)為腎小管細(xì)胞溶酶體增多。其中以高尿酸組(2、3組)腎臟損傷最輕,低尿酸組及高尿酸組(5、6組)損傷較重。結(jié)論:(1)利用酵母膏20g/kg聯(lián)合氧嗪酸鉀200mg-300mg/kg能建立較穩(wěn)定的高尿酸大鼠模型。(2)給予苯溴馬隆能降低正常大鼠血清尿酸水平,增加機體抗氧化能力,但合并明顯腎臟損傷。(3)尿酸水平與腎損傷程度呈“U”型曲線關(guān)系,適當(dāng)升高尿酸水平,能增高大鼠抗氧化能力,降低腎臟損傷程度;過高尿酸水平其抗氧化能力降低,腎臟損傷嚴(yán)重。
[Abstract]:Objective: to understand the effects of different levels of high uric acid on serum antioxidant capacity and renal injury in rats, and to provide help for the establishment of a stable animal model of hyperuricemia. To explore the effect of low uric acid level on rats.) to explore an optimal range of uric acid control, and to provide a basis for the prevention and treatment of clinical diseases in the future. Methods Sixty-four male Sprague-Dawley rats were randomly divided into 8 groups: the first group (control group) was given distilled water daily, the second group (low uric acid group) was treated with 25mg/kg daily. The third group (hyperuricemia group 1) was fed with 20g/kg yeast extract 100mg/kg daily and the fourth group (hyperuricemia group 2) with 20g/kg yeast extract 200mg/kg daily. The fifth group (high uric acid group 3) was perfused with 20g/kg yeast extract 300mg/kg daily and the sixth group (high uric acid group 4) with 20g/kg yeast extract 400mg/kg daily. The seventh group (high uric acid group 5) was perfused with 20g/kg yeast extract 500mg/kg daily, and the eighth group (high uric acid group 6) with 20g/kg yeast extract 600mg/kg daily. During the experiment, rats were weighed daily and adjusted according to their body weight to collect blood from the medial canthus vein once a week. Serum samples were collected from UAA, urea nitrogen bun, creatinine, superoxide dismutase (SOD), glutathione peroxidase (GSH-PXN) and malondialdehyde (MDA.4) for six weeks. It was used for HE staining and electron microscope observation. Results: the UA level in the low uric acid group was significantly lower than that in the control group, and the UA level in all the high uric acid groups was slightly decreased after the second week of modeling and maintained at a higher level. The Cr of control group, low uric acid group, high uric acid group and high uric acid group were not significantly changed in the course of modeling, and Cr in high uric acid group was slightly higher than that in control group at the second week. During the first week of modeling, Cr increased slightly compared with the control group, and reached the peak in the second week. At the fourth week of model making, the level of BUN was basically reduced to the level of control group. (3) during the course of modeling, the BUN of low uric acid group was not significantly abnormal in the control group. BUN was maintained at a higher level during modeling in all high uric acid groups.) the antioxidant capacity of each group was measured: no significant changes were found in the control group during modeling. During the course of modeling, the serum levels of GSH-PX in low uric acid group and high uric acid group were slightly lower than those in control group. Compared with the control group, the serum SODD-GSH-PX level was significantly higher than that in the control group (P < 0.05). Renal pathology: glomerular and renal interstitial congestion and tubule dilatation were observed under light microscope in the low uric acid group and all the hyperuricemia groups. The infiltration of interstitial cells with fibrosis was observed under electron microscope and the number of lysosomes in renal tubule cells was increased. The renal injury was the least in the high uric acid group, and the most serious in the low uric acid group and the high uric acid group. Conclusion the stable rat model of hyperuricemia can be established by yeast extract 20g/kg combined with potassium oxazinate (200mg-300mg/kg). Benzbromarone can decrease the level of serum uric acid and increase the antioxidant capacity of normal rats. However, the relationship between the level of uric acid and the degree of renal injury was "U" curve. If the level of uric acid was raised appropriately, the antioxidant capacity of rats could be increased and the degree of renal injury could be decreased. Kidney damage is severe.
【學(xué)位授予單位】：川北醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R589.7

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