自发性糖尿病肾病食蟹猴生化与肾脏显微形态学的比较研究

发布时间：2018-11-19 13:17

【摘要】：糖尿病肾病作为一个慢性疾病,是一个缓慢逐步的过程,在人为干预引发的糖尿病肾病动物模型之中,因为缺乏这一发展累计过程,因此与自发性的糖尿病肾病有着很大区别。食蟹猴作为非人灵长类,其生化指标抑或生理结构都与人极为相似,而且,和人类相似地,食蟹猴群也存在大量的自发性糖尿病肾病,是以,自发性糖尿病肾病食蟹猴是一个理想的疾病研究动物模型,开展食蟹猴自发性糖尿病肾病研究对人类糖尿病肾病的基础和临床探讨都有积极的参考意义。但目前关于食蟹猴糖尿病肾病的研究,大多是利用人工干预疾病模型,几乎没有食蟹猴自发性糖尿病肾病的研究论文。本研究我们以自发性的糖尿病肾病食蟹猴作为研究对象,并以空腹血糖(FBG) 5.56mmol/L和尿微量白蛋白/尿肌酐(ACR) 17mg/g为阈值进行食蟹猴对照、糖尿病和糖尿病肾病不同组别的划分。之后,对各组别之间的血常规和生化指标进行显著性分析,筛选出与食蟹猴糖尿病肾病具有显著关系的特征指标。进一步地,通过静脉注射糖耐量实验及活检肾组织的免疫组化、显微形态学、超微形态学等特征进行相关分析,以验证分组阈值标准的可行性。结果显示：以FBG 5.56mmol/L以及ACR 17mg/g为阈值标准为基础划分出的各组之间,血糖指标、血脂指标、肝胆功能指标、蛋白尿指标以及肾组织活检中的肾小球基底膜厚度指标、足细胞密度指标、肾小球硬化指数指标具有和人临床结果相类似的病理显著差异性。上述研究分析提示：'FBG 5.56mmol/L 和 ACR 17mg/g"作为食蟹猴糖尿病肾病的诊断阈值是可行的；食蟹猴自发性糖尿病肾病临床指标表现与人的临床表现有很好的一致性；自发性糖尿病肾病食蟹猴可以作为人糖尿病肾病研究的良好动物模型；本研究为进一步的人类糖尿病肾病临床前研究提供了具参考意义的信息。
[Abstract]:Diabetic nephropathy, as a chronic disease, is a slow and gradual process. In the animal model of diabetic nephropathy induced by human intervention, due to the lack of this cumulative process of development, it is very different from spontaneous diabetic nephropathy. As non-human primates, crab-eating monkeys have very similar biochemical indexes or physiological structures to humans, and, like humans, there are a large number of spontaneous diabetic nephropathy in the herbivorous monkeys. Spontaneous diabetic nephropathy is an ideal animal model for the study of disease. The study of spontaneous diabetic nephropathy of crab monkey has positive reference significance for the basic and clinical study of human diabetic nephropathy. However, most of the studies on diabetic nephropathy in crab-eating monkeys are based on artificial intervention models, and there are almost no papers on spontaneous diabetic nephropathy in crab-eating monkeys. In this study, we used spontaneous diabetic nephropathy monkey as the study object, and fasting blood glucose (FBG) 5.56mmol/L) and urinary microalbumin / creatinine (ACR) 17mg/g) as the threshold value of the control crab monkey. The division of different groups of diabetes and diabetic nephropathy. After that, the blood routine and biochemical indexes of each group were analyzed significantly, and the characteristic indexes which had significant relationship with diabetic nephropathy of crab-eating monkey were screened out. In order to verify the feasibility of grouping threshold standard, the correlation analysis was carried out by intravenously glucose tolerance test and biopsy of renal tissue, such as immunohistochemistry, micromorphology, ultramorphology and so on. The results showed that the blood glucose index, blood lipid index, hepatobiliary function index, proteinuria index and glomerular basement membrane thickness index in renal biopsy were divided according to the threshold criteria of FBG 5.56mmol/L and ACR 17mg/g. The index of podocyte density and glomerulosclerosis index had significant difference from the clinical results of human. The results show that: 'FBG 5.56mmol/L and ACR 17mg/g' is feasible as the diagnostic threshold of diabetic nephropathy in crab-eating monkeys, and the clinical manifestations of spontaneous diabetic nephropathy in crab-eating monkeys are in good agreement with the clinical manifestations of human. Spontaneous diabetic nephropathy can be used as a good animal model for the study of human diabetic nephropathy, and this study provides valuable information for further preclinical study of human diabetic nephropathy.
【学位授予单位】：云南大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R587.2;R692.9

【相似文献】