Beharry Kay D A, Modanlou Houchang D, Hasan Jamal, Gharraee Zahra, Abad-Santos Patricia, Sills Jeremy H, Jan Amanda, Nageotte Stephen, Aranda Jacob V
Department of Pediatrics, Division of Neonatal-Perinatal Medicine, University of California Irvine, Irvine, and Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Miller Children's Hospital, Long Beach, California, USA.
Invest Ophthalmol Vis Sci. 2006 Jul;47(7):3036-43. doi: 10.1167/iovs.06-0057.
Ibuprofen and indomethacin are nonselective prostaglandin synthetase inhibitors that have been shown to improve oxygen-induced retinopathy in mice. Vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF)-I, and growth hormone (GH) are potent growth factors involved in retinal development. This study was conducted to examine and compare the effects of early postnatal ibuprofen and indomethacin on ocular and systemic VEGF, IGF-I, and GH during rat ocular development.
Newborn rats were treated with intraperitoneal injections of low and high doses of ibuprofen or indomethacin at birth (postnatal day [P]1) and on P2 and P3. A control group received equivalent volumes of saline. At P14, vitreous fluid, retinal homogenates, and serum were analyzed for VEGF, IGF-I, and GH protein levels. Retinal mRNA expression of VEGF splice variants (VEGF188, VEGF164, VEGF120), VEGF receptors (VEGFR-1, VEGFR-2, Npn-1, Npn-2), and pigment epithelium-derived factor (PEDF) were also examined.
Animals treated with high-dose ibuprofen had significantly lower somatic growth and higher serum and vitreous IGF-I levels. High-dose ibuprofen decreased retinal VEGF levels and retinal VEGF164, VEGF120, and VEGFR-2 transcripts, resulting in a significant increase in the cecal period in 87% of rats at P14. Both indomethacin doses suppressed retinal VEGF164 transcripts without affecting VEGF receptors.
Ibuprofen may be more effective than indomethacin for suppression of retinal VEGF signaling, suggesting a possible therapy for retinal neovascularization. However, deficits in somatic growth concurrent with higher systemic IGF-I levels suggests decreased IGF-I bioactivity. These adverse effects should be considered.
布洛芬和吲哚美辛是非选择性前列腺素合成酶抑制剂，已被证明可改善小鼠氧诱导性视网膜病变。血管内皮生长因子（VEGF）、胰岛素样生长因子（IGF）-I和生长激素（GH）是参与视网膜发育的强效生长因子。本研究旨在检查和比较出生后早期布洛芬和吲哚美辛对大鼠眼部发育过程中眼内和全身VEGF、IGF-I和GH的影响。
新生大鼠在出生时（出生后第[P]1天）、P2和P3接受腹腔注射低剂量和高剂量的布洛芬或吲哚美辛。对照组接受等量的生理盐水。在P14时，分析玻璃体液、视网膜匀浆和血清中的VEGF、IGF-I和GH蛋白水平。还检测了VEGF剪接变体（VEGF188、VEGF164、VEGF120）、VEGF受体（VEGFR-1、VEGFR-2、Npn-1、Npn-2）和色素上皮衍生因子（PEDF）的视网膜mRNA表达。
高剂量布洛芬治疗的动物体生长显著降低，血清和玻璃体IGF-I水平升高。高剂量布洛芬降低了视网膜VEGF水平以及视网膜VEGF164、VEGF120和VEGFR-2转录本，导致87%的大鼠在P14时盲肠期显著增加。两种剂量的吲哚美辛均抑制视网膜VEGF164转录本，而不影响VEGF受体。
布洛芬在抑制视网膜VEGF信号传导方面可能比吲哚美辛更有效，提示可能是一种治疗视网膜新生血管形成的方法。然而，体生长缺陷与全身IGF-I水平升高同时出现表明IGF-I生物活性降低。应考虑这些不良反应。
