Vlasic V, Simakajornboon N, Gozal E, Gozal D
Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville School of Medicine, 570 S. Preston Street, Louisville, KY 40202, U.S.A.
Pediatr Res. 2001 Aug;50(2):236-41. doi: 10.1203/00006450-200108000-00012.
The temporal trajectory of platelet-derived growth factor (PDGF)-beta receptor activation within the dorsocaudal brainstem parallels that of the mild hypoxic ventilatory depression (HVD) seen in adult rats. We hypothesized that enhanced PDGF-beta receptor activity may account for the particularly prominent HVD of developing mammals. To study this issue, 2-, 5-, 10-, and 20-d-old rats underwent hypoxic challenges (10% O(2) for 30 min) after pretreatment with either vehicle (Veh) or the selective PDGF-beta receptor antagonist CGP57148B (intraperitoneal 100 mg/kg). The developmental characteristics and magnitude of the peak hypoxic ventilatory response (HVR) were not modified by the PDGF-beta receptor blocker. However, HVD was markedly attenuated by CGP57148B, and such effect, although still present, gradually abated with increasing postnatal age [p < 0.001, analysis of variance (ANOVA)]. Hypercapnic ventilatory responses were not affected by CGP57148B. The expression of PDGF-beta receptor in the dorsocaudal brainstem was assessed by immunoblotting and confirmed progressively decreasing expression with maturation. We conclude that PDGF-beta receptor activation during hypoxia is an important contributor to HVD at all postnatal ages but more particularly in the immature rat.
血小板衍生生长因子（PDGF）-β受体在成年大鼠背尾侧脑干内的激活时间轨迹与轻度低氧性通气抑制（HVD）的时间轨迹平行。我们推测，增强的PDGF-β受体活性可能是发育中哺乳动物特别显著的HVD的原因。为了研究这个问题，对2日龄、5日龄、10日龄和20日龄的大鼠在预先给予溶剂（Veh）或选择性PDGF-β受体拮抗剂CGP57148B（腹腔注射100mg/kg）后进行低氧挑战（10%氧气，持续30分钟）。PDGF-β受体阻滞剂未改变低氧通气反应（HVR）峰值的发育特征和幅度。然而，CGP57148B显著减弱了HVD，并且这种作用虽然仍然存在，但随着出生后年龄的增加逐渐减弱[p<0.001，方差分析（ANOVA）]。高碳酸血症通气反应不受CGP57148B影响。通过免疫印迹评估背尾侧脑干中PDGF-β受体的表达，并证实其表达随着成熟而逐渐降低。我们得出结论，低氧期间PDGF-β受体的激活是所有出生后年龄HVD的重要促成因素，但在未成熟大鼠中尤为明显。
