Huang Xuerong, Wang Yajuan, Yang Guangran, Yang Zixin, Zhang Jingshang
Department of Neonatology, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China.
Zhonghua Er Ke Za Zhi. 2016 Feb;54(2):131-6. doi: 10.3760/cma.j.issn.0578-1310.2016.02.012.
To investigate whether propranolol application as collyrium or intraperitoneal (IP) injection can promote the recovery of oxygen-induced retinopathy (OIR).
Thirty-six 7-day-old mice were divided into the following 6 groups: normal control, propranolol eye drops, propranolol IP injection, eye drops negative control, IP injection negative control, and pathological model with 6 mice in each. In a typical model of OIR, litters of mice pups with their nursing mothers were exposed to an infant incubator to high oxygen concentration (75 ± 5)% between postnatal day (PD) 7 and PD12, prior to returning to room air. Two routes of propranolol treatment were assessed from PD12 to PD17: IP injection and eye drop, with doses 2 mg/(kg·time), three times a day. Another three groups were given citric acid buffer eye drops, IP injection of citric acid buffer, and negative control were not treated with any drug. Neonatal mice fed in normal conditions served as normal control. Mice were sacrificed at PD17 to evaluate the morphological changes of retinal vessels by fluorescein isothiocyanate-dextran perfusion and retinal whole mount. The retinal neovascularization was evaluated by counting the number of nuclei of the endothelial cell breaking through the internal limiting membrane (ILM).
Compared with the oxygen-exposed group, the branches of retinal vessels went normal with a less un-perfused area in the propranolol eye drops and propranolol IP injection groups [(38.9 ± 9.9)% and (5.6 ± 2.3)% vs. (16.2 ± 10.0)% and (2.2 ± 0.8)%, (25.9 ± 5.0)% and (2.1 ± 2.7)%, F=36.12 and 14.55, P both<0.001]. The number of nuclei of endothelial cells breaking through the ILM on the retinal cross-section in the propranolol eye drops group decreased (14.2 ± 5.1) per slide, which was less than that in the oxygen-exposed group (49.1 ± 8.9) per slide and the propranolol IP injection group (18.0 ± 5.9) per slide; it was also less than that in the eye drops negative control group (47.4 ± 8.1) per slide (F=187.60, P<0.05). Moreover, the number of nuclei of endothelial cells breaking through the ILM on the retinal cross-section in the propranolol IP injection group was less than that in the IP injection negative control group (49.9 ± 7.1) per slide (P<0.05).
Propranolol could effectively inhibit the formation of retinal neovascularization in mice; the eye drops was more effective than the IP injection.
研究普萘洛尔作为滴眼液或腹腔注射是否能促进氧诱导性视网膜病变(OIR)的恢复。
将36只7日龄小鼠分为以下6组:正常对照组、普萘洛尔滴眼液组、普萘洛尔腹腔注射组、滴眼液阴性对照组、腹腔注射阴性对照组和病理模型组,每组6只。在典型的OIR模型中,将一窝窝带哺乳母鼠的幼鼠在出生后第7天(PD)至第12天置于婴儿培养箱中,使其暴露于高氧浓度(75±5)%的环境中,之后再放回室内空气中。从PD12至PD17评估普萘洛尔的两种给药途径:腹腔注射和滴眼液,剂量为2mg/(kg·次),每天3次。另外三组分别给予柠檬酸缓冲液滴眼液、腹腔注射柠檬酸缓冲液,阴性对照组不给予任何药物。在正常条件下饲养的新生小鼠作为正常对照组。在PD17处死小鼠,通过异硫氰酸荧光素-葡聚糖灌注和视网膜铺片评估视网膜血管的形态变化。通过计数突破内界膜(ILM)的内皮细胞核数量评估视网膜新生血管形成情况。
与高氧暴露组相比,普萘洛尔滴眼液组和普萘洛尔腹腔注射组视网膜血管分支恢复正常,未灌注区域减少[(38.9±9.9)%和(5.6±2.3)% vs.(16.2±10.0)%和(2.2±0.8)%,(25.9±5.0)%和(2.1±2.7)%,F=36.12和14.55,P均<0.001]。普萘洛尔滴眼液组视网膜横截面上突破ILM的内皮细胞核数量减少,每张切片为(14.2±5.1)个,少于高氧暴露组每张切片的(49.1±8.9)个和普萘洛尔腹腔注射组每张切片的(18.0±5.9)个;也少于滴眼液阴性对照组每张切片的(47.4±8.1)个(F=187.60,P<0.05)。此外,普萘洛尔腹腔注射组视网膜横截面上突破ILM的内皮细胞核数量少于腹腔注射阴性对照组每张切片的(49.9±7.1)个(P<0.05)。
普萘洛尔可有效抑制小鼠视网膜新生血管形成;滴眼液比腹腔注射更有效。