Hyperoxia-induced airflow restriction and Renin-Angiotensin System expression in a bronchopulmonary dysplasia mouse model.
Hyperoxia-induced airflow restriction and Renin-Angiotensin System expression in a bronchopulmonary dysplasia mouse model.
复制标题
DOI：
10.14814/phy2.15895
复制
发表时间：
2024-01
影响因子：
2.5
通讯作者：
中科院分区：
文献类型：
--
作者：
小儿肺部疾病支气管肺发育不良（BPD）中高氧引起的气流受限的机制尚不清楚。我们假设肾素-血管紧张素系统 (RAS) 活性在 BPD 中发挥作用。 RAS 由血管紧张素转换酶 2 (ACE2) 和血管紧张素 II 受体 2 (AT2) 组成的促发育途径以及由血管紧张素 II 受体 1 (AT1) 介导的促纤维化途径组成。我们在 BPD 小鼠模型中研究了新生儿高氧血症、气流受限和 RAS 活性之间的关联。 C57 幼鼠被随机分配到常氧 (FiO2 = 0.21) 或高氧 (FiO2 = 0.75) 条件下，为期 15 天 (P1–P15)。在 P15、P20 和 P30，我们使用体积描记法测量气流受限，并通过聚合酶链反应和蛋白质印迹测量 ACE2、AT1 和 AT2 mRNA 和蛋白质表达。高氧增加气流限制 P15 和 P20，减少 ACE2 和 AT2 mRNA，减少 AT2 蛋白，增加 AT1 蛋白表达。 ACE2 mRNA 和蛋白质在 P20 时仍受到抑制。到 P30 时，气流限制和 RAS 表达在各组之间没有差异。在我们的 BPD 小鼠模型中，高氧导致气流受限，促纤维化 RAS 通路的肺部表达增加，并降低促发育通路的表达。这些相关发现可能表明 RAS 在高氧引起的气流受限中具有因果作用。新生儿高氧血症后肾素-血管紧张素系统表达和气流受限标志物的纵向变化。
Mechanisms underlying hyperoxia‐induced airflow restriction in the pediatric lung disease Bronchopulmonary dysplasia (BPD) are unclear. We hypothesized a role for Renin‐Angiotensin System (RAS) activity in BPD. RAS is comprised of a pro‐developmental pathway consisting of angiotensin converting enzyme‐2 (ACE2) and angiotensin II receptor type 2 (AT2), and a pro‐fibrotic pathway mediated by angiotensin II receptor type 1 (AT1). We investigated associations between neonatal hyperoxia, airflow restriction, and RAS activity in a BPD mouse model. C57 mouse pups were randomized to normoxic (FiO2 = 0.21) or hyperoxic (FiO2 = 0.75) conditions for 15 days (P1–P15). At P15, P20, and P30, we measured airflow restriction using plethysmography and ACE2, AT1, and AT2 mRNA and protein expression via polymerase chain reaction and Western Blot. Hyperoxia increased airflow restriction P15 and P20, decreased ACE2 and AT2 mRNA, decreased AT2 protein, and increased AT1 protein expression. ACE2 mRNA and protein remained suppressed at P20. By P30, airflow restriction and RAS expression did not differ between groups. Hyperoxia caused high airflow restriction, increased pulmonary expression of the pro‐fibrotic RAS pathway, and decreased expression of the pro‐developmental in our BPD mouse model. These associated findings may point to a causal role for RAS in hyperoxia‐induced airflow restriction. Longitudinal changes in Renin‐Angiotensin System expression and markers of airflow restriction following neonatal hyperoxia.
影响因子：
2.9
作者：
Ryckman, K. K.;Dagle, J. M.;Kelsey, K.;Momany, A. M.;Murray, J. C.
通讯作者：
Murray, J. C.
影响因子：
3.6
作者：
Shefali-Patel D;Paris MA;Watson F;Peacock JL;Campbell M;Greenough A
通讯作者：
Greenough A
影响因子：
3.6
作者：
Oarhe, Chinyere I.;Vinh Dang;MyTrang Dang;Hang Nguyen;Gopallawa, Indiwari;Gewolb, Ira H.;Uhal, Bruce D.
通讯作者：
Uhal, Bruce D.