高尿酸血癥大鼠模型初探
發(fā)布時間：2018-09-19 11:24
【摘要】：高尿酸血癥是由于嘌呤代謝紊亂和/或尿酸排泄減少所引起的一組異質(zhì)性疾病,以血尿酸升高為主要特征,可分為原發(fā)性和繼發(fā)性兩種,其中,原發(fā)性高尿酸血癥占絕大多數(shù)。近年來,高尿酸血癥的發(fā)病率呈現(xiàn)逐年增高的趨勢,但其病因及發(fā)病機(jī)制目前尚不清楚。對于此類疾病的研究,合適的動物模型是基礎(chǔ),但由于常用實驗動物如大、小鼠體內(nèi)存在尿酸酶使之嘌呤分解代謝途徑與人類不同,為高尿酸血癥動物模型的建立帶來了巨大困難。目前常用的造模方法主要包括直接補(bǔ)充尿酸前體物質(zhì)或者外源性尿酸、消除或者抑制尿酸酶的活性、抑制腎臟對尿酸的排泄等,這些方法各有特色,但維持時間短,腎臟損傷出現(xiàn)早且嚴(yán)重,與人類原發(fā)性高尿酸血癥的發(fā)生發(fā)展仍有一定差距,故如何建立同人體異常尿酸代謝一致的、穩(wěn)定持久的高尿酸血癥動物模型,仍值得不斷的理論研究和實驗探索。本實驗擬采用果糖與氧嗪酸鉀聯(lián)合應(yīng)用,以期在大鼠體內(nèi)建立穩(wěn)定、持久、肝腎損傷小的高尿酸血癥模型,為此類疾病的研究、治療藥物的篩選等提供合適的動物模型。1.探討5%果糖+OAPS能否用于高尿酸血癥大鼠模型的建立。雄性SD大鼠15只,隨機(jī)分為空白組(n=5)、10%果糖+OAPS組(n=5)和5%果糖+OAPS組(n=5)。空白組給予標(biāo)準(zhǔn)飲食,10%果糖+OAPS組給予標(biāo)準(zhǔn)飼料和10%果糖水,且每日分別兩次皮下注射OAPS乳懸液100mg/(kg.d),5%果糖+OAPS組給予標(biāo)準(zhǔn)飼料和5%果糖水,且每日分別兩次皮下注射OAOS乳懸液100mg/(kg.d),各組大鼠均自由飲食飲水,持續(xù)13周,于不同時間點斷尾取血檢測大鼠血清UA、BUN、Cr水平,結(jié)束時取大鼠肝、腎做病理組織切片。其結(jié)果表明5%果糖+OAPS能用于高尿酸血癥動物模型的建立。2.探討5%果糖+OAPS聯(lián)合應(yīng)用建立高尿酸血癥動物模型的持久性、穩(wěn)定性及肝腎損傷。雄性SD大鼠40只,隨機(jī)分為空白組(n=10)、5%果糖+OAPS組(n=10)、5%果糖組(n=10)、OAPS組(n=10),空白組給予標(biāo)準(zhǔn)飲食,5%果糖+OAPS組給予5%果糖水+早晚皮下注射OAPS乳懸液100 mg/(kg.d),5%果糖組給予5%果糖水,OAPS組早晚皮下注射OAPS乳懸液100 mg/(kg.d),各組大鼠均自由飲食飲水,持續(xù)18周,于不同時間點取血檢測大鼠血清UA、BUN、Cr水平,結(jié)束時取大鼠肝、腎做病理組織切片。第1周時,5%果糖+OAPS組血清UA即顯著高于其他各組(P均0.01),持續(xù)穩(wěn)定至18周,5%果糖組、OAPS組僅第2周時血清UA高于空白組(P0.01),血清BUN、Cr水平實驗組與空白組比較差異均無統(tǒng)計學(xué)意義(P0.05),肝、腎組織切片觀察未見明顯損傷。這表明5%果糖水與OAPS聯(lián)合應(yīng)用能建立穩(wěn)定持久幾乎未見肝腎損傷的高尿酸血癥動物模型。
[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.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R589.7;R-332
本文編號：2249993
[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.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R589.7;R-332
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