高尿酸血症大鼠模型初探

发布时间：2018-09-19 11:24

【摘要】：高尿酸血症是由于嘌呤代谢紊乱和/或尿酸排泄减少所引起的一组异质性疾病,以血尿酸升高为主要特征,可分为原发性和继发性两种,其中,原发性高尿酸血症占绝大多数。近年来,高尿酸血症的发病率呈现逐年增高的趋势,但其病因及发病机制目前尚不清楚。对于此类疾病的研究,合适的动物模型是基础,但由于常用实验动物如大、小鼠体内存在尿酸酶使之嘌呤分解代谢途径与人类不同,为高尿酸血症动物模型的建立带来了巨大困难。目前常用的造模方法主要包括直接补充尿酸前体物质或者外源性尿酸、消除或者抑制尿酸酶的活性、抑制肾脏对尿酸的排泄等,这些方法各有特色,但维持时间短,肾脏损伤出现早且严重,与人类原发性高尿酸血症的发生发展仍有一定差距,故如何建立同人体异常尿酸代谢一致的、稳定持久的高尿酸血症动物模型,仍值得不断的理论研究和实验探索。本实验拟采用果糖与氧嗪酸钾联合应用,以期在大鼠体内建立稳定、持久、肝肾损伤小的高尿酸血症模型,为此类疾病的研究、治疗药物的筛选等提供合适的动物模型。1.探讨5%果糖+OAPS能否用于高尿酸血症大鼠模型的建立。雄性SD大鼠15只,随机分为空白组(n=5)、10%果糖+OAPS组(n=5)和5%果糖+OAPS组(n=5)。空白组给予标准饮食,10%果糖+OAPS组给予标准饲料和10%果糖水,且每日分别两次皮下注射OAPS乳悬液100mg/(kg.d),5%果糖+OAPS组给予标准饲料和5%果糖水,且每日分别两次皮下注射OAOS乳悬液100mg/(kg.d),各组大鼠均自由饮食饮水,持续13周,于不同时间点断尾取血检测大鼠血清UA、BUN、Cr水平,结束时取大鼠肝、肾做病理组织切片。其结果表明5%果糖+OAPS能用于高尿酸血症动物模型的建立。2.探讨5%果糖+OAPS联合应用建立高尿酸血症动物模型的持久性、稳定性及肝肾损伤。雄性SD大鼠40只,随机分为空白组(n=10)、5%果糖+OAPS组(n=10)、5%果糖组(n=10)、OAPS组(n=10),空白组给予标准饮食,5%果糖+OAPS组给予5%果糖水+早晚皮下注射OAPS乳悬液100 mg/(kg.d),5%果糖组给予5%果糖水,OAPS组早晚皮下注射OAPS乳悬液100 mg/(kg.d),各组大鼠均自由饮食饮水,持续18周,于不同时间点取血检测大鼠血清UA、BUN、Cr水平,结束时取大鼠肝、肾做病理组织切片。第1周时,5%果糖+OAPS组血清UA即显著高于其他各组(P均0.01),持续稳定至18周,5%果糖组、OAPS组仅第2周时血清UA高于空白组(P0.01),血清BUN、Cr水平实验组与空白组比较差异均无统计学意义(P0.05),肝、肾组织切片观察未见明显损伤。这表明5%果糖水与OAPS联合应用能建立稳定持久几乎未见肝肾损伤的高尿酸血症动物模型。
[Abstract]:Hyperuricemia is a group of heterogeneous diseases caused by purine metabolic disorder and / or reduction of uric acid excretion. Hyperuricemia is characterized by elevated serum uric acid, which can be divided into primary and secondary ones, among which primary hyperuricemia accounts for the majority. In recent years, the incidence of hyperuricemia is increasing year by year, but its etiology and pathogenesis are still unclear. Suitable animal models are the basis for the study of these diseases, but due to the presence of uric acid enzymes in mice, the purine catabolism pathway is different from that of human beings due to the presence of uric acid enzymes in mice due to common laboratory animals such as large animals. It has brought great difficulties for the establishment of animal model of hyperuricemia. The commonly used modeling methods include direct supplementation of uric acid precursor or exogenous uric acid, elimination or inhibition of the activity of uric acid enzyme, inhibition of renal excretion of uric acid, etc. These methods have their own characteristics, but their duration is short. Kidney injury appeared early and severe, and there was still a certain gap between the occurrence and development of human primary hyperuricemia, so how to establish a stable and persistent animal model of hyperuricemia consistent with human abnormal uric acid metabolism. It is still worthy of continuous theoretical research and experimental exploration. In this study, fructose combined with potassium oxazinate was used in order to establish a stable, lasting hyperuricemia model with little liver and kidney damage in rats, and to provide a suitable animal model for the study of such diseases and the screening of therapeutic drugs. To investigate whether 5% fructose OAPS can be used to establish rat model of hyperuricemia. Fifteen male SD rats were randomly divided into two groups: blank group (n = 5), 10% fructose OAPS group (n = 5) and 5% fructose OAPS group (n = 5). The blank group was given standard diet 10% fructose OAPS group and 10% fructose water, and the OAPS milk suspension 100mg/ (kg.d) 5% fructose OAPS group was given standard feed and 5% fructose water twice a day. OAOS milk suspension 100mg/ (kg.d) was injected subcutaneously twice a day. The rats in each group were fed and drank freely for 13 weeks. The serum UA,BUN,Cr level was measured at different time points by severed blood. At the end of the experiment, the liver and kidney of the rats were taken for pathological sections. The results showed that 5% fructose OAPS could be used to establish animal model of hyperuricemia. To study the persistence, stability and liver and kidney injury of hyperuricemia animal model with 5% fructose OAPS. 40 male SD rats, They were randomly divided into 5% fructose OAPS group and 5% fructose OAPS group. The blank group was given 5% fructose water and 5% fructose water was subcutaneously injected with 5% fructose water sooner or later. The 5% fructose water group was subcutaneously injected subcutaneously with 5% fructose water in 5% fructose water. OAPS milk suspension was injected with 100 mg/ (kg.d), and the rats in each group were fed and drank freely. After 18 weeks, the serum UA,BUN,Cr level was measured at different time points, and the liver and kidney were taken for pathological sections at the end of the experiment. At the first week, the serum UA of 5% fructose OAPS group was significantly higher than that of the other groups (all P 0.01), and the serum UA of the 5% fructose group was higher than that of the blank group only at the 2nd week (P0.01). There was no difference in serum BUN,Cr level between the experimental group and the blank group. Statistical significance (P0.05), liver, No obvious injury was observed in renal tissue sections. This indicated that 5% fructose water combined with OAPS could establish a stable and lasting hyperuricemia animal model with little liver and kidney injury.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R589.7;R-332

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