高温高湿环境诱导建立高尿酸血症大鼠模型及其主要器官病理学特征 研究

The study on establishing hyperuricemia rat model induced by high-temperature-humidity environment and pathological characteristics of its vital organs

  • 摘要:
    背景 南方沿海高温高湿环境下居民高尿酸血症呈现高发现状。目的 建立高温高湿环境致高尿酸血症动物模型,并探讨其肾脏、肝脏、踝关节等病理改变。方法 雄性SD大鼠30只,随机分为空白对照组(control group,CON)、氧嗪 酸 钾 组(potassium oxonate group,PO)、高 嘌 呤 饮 食 组(high purine diet group,HPD)、高 温 高 湿 组(high temperaturehumidity group,HT)和复合因素组(compound factors group,CF),每组6只。CON组仅予以0.5%羧甲基纤维素钠溶液灌胃,PO组以250mg/kg氧嗪酸钾混悬液灌胃,HPD组为250mg/kg氧嗪酸钾混悬液灌胃+20%酵母饲料喂养,HT组和CF组分别为在PO组、HPD组干预基础上,进行高温高湿环境处理,通过温度为37±0.5℃、相对湿度为80±1%的特定恒温培养箱进行照射,1 h/d,造模持续12周。分别于0周、6周和12周时采血检测血清尿酸水平,第6周、12周时每组随机选取3只大鼠解剖取材,通过HE染色评估该新型高尿酸血症大鼠模型肾脏、肝脏、踝关节等重要组织器官的病理学改变。结果 (1)造模6周后,PO组、HPD组、HT组、CF组血尿酸水平显著高于CON组(P<0.05),且HT组高于PO组、CF组高于HPD组(P <0.05);(2)本实验发现PO组和HPD肾脏组织形态表现为肾小管扩张,而HT和CF组出现大量近曲小管上皮细胞肿胀,管腔间隙变窄,部分小管间隙显著炎性浸润,此外CF组还存在部分肾小管上皮细胞萎缩。(3)光镜下可见PO组和HPD组肝血窦轻度扩张,而HT组和CF组肝细胞肿胀、肝血窦变窄,CF组心肌纤维排列稍紊乱、踝关节软骨层结构欠平滑,其余组织结构未见明显异常。(4)造模6周时可见HPD组、HT组和CF组存在尿酸盐晶体沉积,其中CF组最重,至12周时HPD组、HT组和CF组晶体沉积均有所减少。结论 通过12周高温高湿环境处理制备的高尿酸血症大鼠模型呈现广泛的肾脏、肝脏、心脏和踝关节的组织形态变化。

     

    Abstract: Abstract: Background There is a high incidence of hyperuricemia among residents in southern coastal areas under high temperature and high humidity environment. Objective To establish an animal model of hyperuricemia caused by high temperature and high humidity environment, and to explore the pathological changes in kidney, liver and ankle joints. Methods A total of 30 SPF-SD male rats were divided into following five groups: control group (CON, n=6), potassium oxonate group (PO, n=6), high purine diet group (HPD, n=6), high temperature-humidity group (HT, n=6), and compound factor group (CF, n=6). The ratsfromCON group were only given 0.5% sodium carboxymethyl cellulose solution by gavage. PO group was gavaged with 250mg/kg potassium oxonate suspension, while HPD group was gavaged with 250mg/kg potassium oxonate suspension and fed with 20% yeast feed. On the basis of the above intervention modeling methods for the PO group and the HPD group, HT group and CF group were treated in high temperature-humidity environment, that is, irradiated in a special constant temperature incubator with a temperature of 37±0.5℃ and a relative humidity of 80±1% for 1 h/d. The experiment lasted for 12 continuous weeks, atthetime of 0 week, 6th week and 12th week all rats were fasted for at least 12h before collecting blood samples so as to test their SUA levels. Three rats from each group were anesthetized to collect their renal, heart, liver and ankle tissues after modeling for 6 weeks and 12 weeks respectively. Results (1) the SUA levels of CF group, HT group, HPD group PO group are significantly higher than that of CON group (P<0.05), and that of HT group was higher than PO group (P<0.05), CF group was higher than HPD group (P<0.05). (2) Inthisstudy, the renal tissue morphology of PO group and HPD group showed tubular dilatation, while there were a large number of epithelial cells of proximal convoluted tubules swelled in HT and CF groups, lead to the lumen gap narrowed, and some tubule spaces showed significant inflammatory infiltration. In addition, some renal tubular epithelial cells atrophy in CF group. (3) Under light microscope, the hepatic sinuses in PO group and HPD group were slightly dilated, while the liver cells in HT group and CF group were swollen and the hepatic sinuses were narrowed. In CF group, the arrangement of myocardial myofilaments was slightly disordered, and the structure of ankle cartilage layer was not smooth, but other tissue structures were not obviously abnormal.(4) At the 6th week of modeling, urate crystals were deposited in HPD group, HT group and CF group, among which CF group was the worst. And at the 12th week, the crystals in HPD group, HT group and CF group all decreased. Conclusions Hyperuricemia rat model prepared by 12-week high-temperature-humidity environment treatment presented extensive changes in the morphology of kidney, liver, heart and ankle joints.

     

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