Department of Pediatrics, College of Medicine, Korea University, Seoul, South Korea.
Department of Pediatrics, Korea University Ansan Hospital, 123, Jeokgeum-ro, Danwon-gu, Ansan-si, Gyeonggi-do, 15355, South Korea.
J Mol Histol. 2018 Apr;49(2):219-228. doi: 10.1007/s10735-018-9762-7. Epub 2018 Feb 13.
Proper and timely assembly of the kidney vasculature with their respective nephrons is crucial during normal kidney development. In this study, we investigated the effects of enalapril (angiotensin-converting enzyme inhibitor) on angiogenesis-related gene expression and microvascular endothelium related to glomeular and tubular changes in the neonatal rat kidney. Enalapril-treated rats had higher tubular injury scores and lower glomerular maturity grades than those of untreated rats. In the enalapril-treated group, intrarenal angiopoietin-2, Tie-2, and thrombospondin-1 protein expression increased, whereas intrarenal angiopoietin-1 protein expression decreased. JG12-positive glomerular and peritubular capillary staining was reduced in the enalapril-treated rat kidney. The number of JG12-positive capillary endothelial cells was directly correlated with glomerular maturation grade and was inversely related with the tubular injury. Our findings suggest the imbalance between pro- and anti-angiogenic factors may be implicated in the loss of capillaries in associated with impaired nephrogenesis after angiotensin II blockade in the developing rat kidney.
在正常肾脏发育过程中，肾脏血管系统及其各自的肾单位的正确和及时组装至关重要。在这项研究中，我们研究了依那普利（血管紧张素转换酶抑制剂）对新生大鼠肾脏中与肾小球和肾小管变化相关的血管生成相关基因表达和微血管内皮的影响。与未治疗的大鼠相比，依那普利治疗的大鼠具有更高的肾小管损伤评分和更低的肾小球成熟度等级。在依那普利治疗组中，肾内血管生成素-2、Tie-2 和血栓素-1 蛋白表达增加，而肾内血管生成素-1 蛋白表达减少。在依那普利治疗的大鼠肾脏中，JG12 阳性肾小球和肾小管周围毛细血管染色减少。JG12 阳性毛细血管内皮细胞的数量与肾小球成熟度等级直接相关，与肾小管损伤呈负相关。我们的研究结果表明，促血管生成和抗血管生成因子之间的失衡可能与血管生成抑制后血管丢失和肾发生受损有关。
