血管生成素样蛋白2在糖尿病肾病小鼠肾脏中的表达研究

Expression of ANGPTL2 in The Kidney of Diabetic Nephropathy db/db Mice

利用半定量RT-PCR和免疫组化的方法同时从mRNA水平和蛋白质水平对血管生成素样蛋白2在不同病理阶段的2型糖尿病肾病模型小鼠——db/db小鼠肾脏中的表达情况进行了较为系统的分析.结果发现:a.在糖尿病前的db/db小鼠(4周龄的db/db小鼠),血管生成素样蛋白2与作为正常对照的db/m小鼠相比,差异不是很大,随着肥胖的加剧,高血糖、蛋白尿的出现,血管生成素样蛋白2在db/db小鼠肾脏中的表达无论从mRNA水平还是从蛋白质水平均显著升高.b.从免疫组化的分析结果来看,血管生成素样蛋白2主要分布于小鼠肾脏的肾小球部分,主要是沿毛细血管袢呈线性分布,其位置与足细胞的位置重叠,足细胞是小鼠肾脏中血管生成素样蛋白2的主要分泌细胞.c.小鼠肾脏血管生成素样蛋白2的表达水平似乎还与鼠龄相关:虽然变化幅度不是很大,但在周龄较大的小鼠(如20周龄以上),其表达水平相对较高.上述工作不仅印证了先前对2型糖尿病肾病患者肾小球基因表达谱的分析结果,更加明确了血管生成素样蛋白2与糖尿病肾病的相关性,同时揭示了血管生成素样蛋白2在正常小鼠和糖尿病肾病小鼠肾脏中的表达、分布和变化规律,有利于进一步揭示血管生成素样蛋白2的功能及其在糖尿病肾病发生、发展过程中的可能作用,探讨糖尿病肾病的分子机制.

Kidney samples were obtained from db/db mice and their db/m littermates at the age of 4, 8, 12, 16, 20 and 24 weeks. The expression of ANGPTL2 was assessed by RT-PCR and immunohistochemistry, and then correlated with biochemical and histological indices of kidney injury. No significant difference of ANGPTL2 expression was found in the kidney of db/db mice and the control db/m mice at the age of 4 weeks, a time when all biochemical and histological indices indicated that the db/db mice were in pre-diabetic condition. However, with the development of obesity, hyperglycemia and proteinuria, the expression of ANGPTL2 in the kidney of db/db mice increased, which indicated that the increased expression of ANGPTL2 associated with diabetic nephropathy. ANGPTL2 protein was found distributed mainly in the glomerulus. It is along the capillary loop, located just outside the basement membrane, and in the same location as podocytes, which suggested that podocytes are the main origin of ANGPTL2 in the kidney. Besides, increased expression of ANGPTL2 was found in older db/m mice though it has not reached to a significant level, which may suggest that ANGPTL2 might have some thing to do with the kidney injury caused by ageing.