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首页> 外文期刊>American Journal of Physiology >Angiotensin-converting enzyme inhibition aggravates renal interstitial injury resulting from partial unilateral ureteral obstruction in the neonatal rat.
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Angiotensin-converting enzyme inhibition aggravates renal interstitial injury resulting from partial unilateral ureteral obstruction in the neonatal rat.

机译：血管紧张素转换酶抑制作用加剧了新生大鼠单侧输尿管部分阻塞所致的肾间质损伤。

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Congenital urinary tract obstruction is the most important cause of renal insufficiency in infants and children, and angiotensin-converting enzyme (ACE) inhibitors attenuate the progression of renal disease in adults. ACE inhibitors are increasingly utilized in children with progressive renal disease. Because angiotensin is necessary for normal renal development, we examined the effects of ACE inhibition both during and immediately following the period of postnatal nephrogenesis in the neonatal rat subjected to sham operation or partial unilateral ureteral obstruction (UUO) under general anesthesia within the first 48 h of life. Rats in group I received enalapril 30 mg/kg body wt (or vehicle) daily for the first 10 days, while in group II, the 10 days of treatment began 10 days after surgery. Kidneys were harvested at day 21 and analyzed for apoptosis (TUNEL), interstitial macrophages (ED-1 immunohistochemistry), myofibroblasts (alpha-smooth muscle actin), and collagen (Sirius red). Partial UUO delayedglomerular maturation and increased ipsilateral renal macrophage infiltration, alpha-smooth muscle actin and Sirius red staining. In group I, enalapril increased myofibroblast accumulation in sham-operated kidneys, but not in obstructed kidneys. In contrast, in group II, enalapril further increased macrophage, myofibroblast, and collagen accumulation following partial UUO. The relative abundance of components of the kallikrein-kinin system, measured by Western blot, was not altered by partial UUO in the 14- and 28-day-old rat. Thus, in contrast to its salutary effects at later ages, ACE inhibition can worsen injury to the partially obstructed kidney during renal maturation even after the completion of nephrogenesis.
机译：先天性尿路阻塞是婴儿和儿童肾功能不全的最重要原因，血管紧张素转换酶（ACE）抑制剂可减轻成人肾脏疾病的进展。 ACE抑制剂越来越多地用于进行性肾脏疾病的儿童。因为血管紧张素对于正常的肾脏发育是必需的，所以我们在出生后48小时内接受全身麻醉的假手术或部分单侧输尿管梗阻（UUO）的新生大鼠中，在产后肾发生期间和之后均检查了ACE抑制的作用生活。第一组的大鼠在头10天内每天接受依那普利30 mg / kg体重（或赋形剂）的服用，而在第二组中，则在术后10天开始接受10天的治疗。在第21天收获肾脏并分析其凋亡（TUNEL），间质巨噬细胞（ED-1免疫组织化学），成肌纤维细胞（α-平滑肌肌动蛋白）和胶原蛋白（天狼星红）。部分UUO延迟肾小球成熟，增加同侧肾巨噬细胞浸润，α平滑肌肌动蛋白和天狼星红染色。在第一组中，依那普利增加了假手术肾脏中成纤维细胞的积累，但在阻塞性肾脏中却没有。相反，在第二组中，依那普利在部分UUO后进一步增加了巨噬细胞，成肌纤维细胞和胶原蛋白的积累。通过蛋白质印迹法测得的激肽释放酶激肽系统组分的相对丰度在14和28天大的大鼠中并未被部分UUO改变。因此，与其在晚年的有益作用相反，即使在肾生成完成后，ACE抑制作用也会使肾脏成熟过程中对部分阻塞的肾脏的损伤加重。

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