血管内皮特异性过表达microRNA-155对大鼠妊娠过程的影响  

Effects of vascular endothelial specific over-expression microRNA-155 on the pregnancy of rats

作　　者：吴梦菲 颜桂军[1] 沈莉[1] 胡娅莉[1] 

机构地区：[1]南京医科大学附属鼓楼临床医学院妇产科,江苏南京210008

出　　处：《南京医科大学学报（自然科学版）》2017年第5期532-538,共7页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(81370724)

摘　　要：目的 :建立血管内皮特异过表达microRNA-155(miR-155)转基因大鼠模型并观察其血压、蛋白尿等表型及妊娠负荷施加后的变化。方法:把外源miR-155基因插入血管内皮细胞特异表达VE-cadherin启动子下游,构建转基因表达载体,将所得载体线性化后,通过受精卵显微注射技术,构建miR-155转基因大鼠,并利用特异引物PCR法鉴定转基因大鼠基因型。通过尾套法、生化检测、组织学检查对未孕和妊娠雌性转基因大鼠的表型进行初步分析。结果:血管内皮特异性过表达miR-155转基因大鼠在胸主动脉、腹主动脉、肾脏、心脏组织miR-155表达较野生型鼠增高2.3、3.3、2.9、3.3倍。未妊娠时miR-155转基因雌性大鼠血压、尿蛋白、血管壁和肾脏结构与非转基因型大鼠比较,差异均无统计学意义。但妊娠后miR-155转基因雌性大鼠血压轻度增高、蛋白尿增加、胎儿生长受限发生率增加,胸/腹主动脉的血管壁结构紊乱和肾小管上皮空泡样变等。结论:血管内皮特异性miR-155转基因大鼠妊娠负荷增加后,表现出子痫前期表型。Objective： To establish a vascular endothelial-specific overexpressed microRNA-155 transgenic rat model; and to observe its blood pressure, proteinuria phenotypes and changes after gestational load application. Methods： The exogenous miR-155 gene was inserted downstream of the VE-cadherin promoter specifical for vascular endothelial cells to construct the transgenic expression vector. After linearization of the vector, the miR-155 transgenic rats were established by zygote microinjection technique. The genotype of transgenic rats was identified by specifical primer PCR. Furthermore, tail-cuff method, biochemical detection and histological examination were used to preliminarily analyze the phenotypes of pregnant and non-pregnant female transgenic rats. Results： The miR-155 expressions in thoracic aorta, abdominal aorta, kidney and heart tissues of the vascular endothelial-specific overexpressed microRNA-155 transgenic rats were 2.3-fold, 3.3-fold, 2.9-fold and 3.3-fold higher than the wild-type rats,respectively. No significant differences were observed in blood pressure, urine protein, vascular wall or kidney structure between the miR-155 transgenic non-pregnant female rats and the non-transgenic rats. However, after pregnancy, the miR-155 transgenic female rats exhibited mildly elevated blood pressure, increased proteinuria, increased incidence of fetal growth restriction, disorderly structure of thoracic/abdominal aortic walls, tubular epithelial vacuolization, etc. Conclusion： After increase of gestational load, the vascular endothelium-specific miR-155 transgenic rats exhibited pre-eclampsia phenotype.

关 键 词：MIR-155 转基因大鼠 血管内皮细胞 子痫前期 

分 类 号：R789[医药卫生—口腔医学]