不同尿酸水平对大鼠血清抗氧化能力及肾脏影响的研究

发布时间：2018-05-20 22:20

本文选题：尿酸 + 动物模型　；参考：《川北医学院》2017年硕士论文

【摘要】：目的:(1)了解不同高尿酸水平对大鼠血清抗氧化能力及肾脏损伤的影响,同时为创建一个稳定的高尿酸动物模型提供帮助。(2)同时建立低尿酸模型,探讨低尿酸水平对大鼠的影响。(3)探讨一种最佳的尿酸控制范围,为将来尿酸对临床疾病的预防及治疗提供一定依据。方法:(1)选取64只雄性SD大鼠随机分成8组。(2)第一组(对照组)每天灌胃蒸馏水;第二组(低尿酸组)每天按照25mg/kg灌胃苯溴马隆;第三组(高尿酸1组)每天按照20g/kg灌胃酵母膏+100mg/kg灌胃氧嗪酸钾;第四组(高尿酸2组)每天按照20g/kg灌胃酵母膏+200mg/kg灌胃氧嗪酸钾;第五组(高尿酸3组)每天按照20g/kg灌胃酵母膏+300mg/kg灌胃氧嗪酸钾;第六组(高尿酸4组)每天按照20g/kg灌胃酵母膏+400mg/kg灌胃氧嗪酸钾;第七组(高尿酸5组)每天按照20g/kg灌胃酵母膏+500mg/kg灌胃氧嗪酸钾;第八组(高尿酸6组)每天按照20g/kg灌胃酵母膏+600mg/kg灌胃氧嗪酸钾;以上药物每日两次灌胃完成,实验期间大鼠每日称重并根据体重调整给药剂量。(3)每周经内眦静脉采血一次,分离出血清进行尿酸(UA)、尿素氮(BUN)、肌酐(Cr)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、丙二醛(MDA)检测。(4)连续采血六周后处死大鼠,分离并切除肾脏,分别用于HE染色、masson特殊染色及电镜观察。结果:(1)各组间UA检测:低尿酸组造模过程中UA较对照组明显降低;所有高尿酸组UA水平均表现为于造模第二周达到高峰后稍下降并维持在较高水平,且UA升高程度与所给药物成剂量依赖性。(2)各组间Cr检测:造模过程中对照组、低尿酸组、高尿酸1组Cr未见明显改变;高尿酸组(2-3组)第二周Cr较对照组轻微升高,于造模第三周基本恢复正常;高尿酸组(4-6组)于造模第一周Cr较对照组稍微升高,造模第二周达到高峰,于造模第四周基本降至对照组水平。(3)各组间BUN检测:造模过程中对照组、低尿酸组BUN未见明显异常;所有高尿酸组造模过程中BUN维持在较高水平。(4)各组间抗氧化能力检测:造模过程中对照组未见明显改变;造模过程中低尿酸组及高尿酸组(1-3组)血清SOD、GSH-PX较对照组升高、MDA较对照组稍低;而高尿酸组(4-6组)血清SOD、GSH-PX较对照组降低,MDA较对照组明显升高。(5)肾脏病理观察:低尿酸组及所有高尿酸组光镜下均表现为肾小球及肾间质充血、肾小管扩张、肾间质炎细胞浸润伴纤维化,电镜下表现为肾小管细胞溶酶体增多。其中以高尿酸组(2、3组)肾脏损伤最轻,低尿酸组及高尿酸组(5、6组)损伤较重。结论:(1)利用酵母膏20g/kg联合氧嗪酸钾200mg-300mg/kg能建立较稳定的高尿酸大鼠模型。(2)给予苯溴马隆能降低正常大鼠血清尿酸水平,增加机体抗氧化能力,但合并明显肾脏损伤。(3)尿酸水平与肾损伤程度呈“U”型曲线关系,适当升高尿酸水平,能增高大鼠抗氧化能力,降低肾脏损伤程度;过高尿酸水平其抗氧化能力降低,肾脏损伤严重。
[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.
【学位授予单位】：川北医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R589.7

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