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虾青素对氧诱导视网膜病变小鼠模型的抗增殖和抗细胞凋亡作用。

Antiproliferative and anti-apoptotic effect of astaxanthin in an oxygen-induced retinopathy mouse model.

机构信息

Department of Ophthalmology, Faculty of Medicine, Baskent University, Ankara, Turkey.

Department of Histology and Embryology, Faculty of Medicine, Baskent University, Ankara, Turkey.

出版信息

Can J Ophthalmol. 2019 Feb;54(1):65-74. doi: 10.1016/j.jcjo.2018.02.017. Epub 2018 Apr 11.

Abstract

OBJECTIVE

To evaluate the impact of intravitreal (IV) and intraperitoneal (IP) astaxanthin (AST) injections on neovascular development (ND), retinal morphology, and apoptotic activity in a C57BL/6J mouse model with hyperoxia-induced retinopathy (HIR).

DESIGN

C57BL/6J mouse model.

METHODS

Two negative control groups (n = 6 each; one of which received IV sterile dimethyl sulfoxide [DMSO]) of C57BL/6J-type mice were exposed to room air. The HIR groups included 36 C57BL/6J-type mice exposed to 75% ± 2% oxygen from postnatal day (PD) 7 to PD 12. On PD 12, these mice were randomized into 6 groups (n = 6 each): 2 HIR control groups (one of which received IV-DMSO), 2 IV-AST groups (10 and 100 µg/mL), and 2 IP-AST groups (0.5 and 5 mg/kg). We measured ND by counting neovascular tufts in cross sections and examined histological, ultrastructural changes via light and electron microscopy. Apoptosis was detected using terminal deoxynucleotidyl transferase-mediated nick end-labeling.

RESULTS

No ND was detected in the negative control groups. ND levels were not significantly different between high- and low-dose AST for either means of administration. However, ND levels were significantly lower in the AST groups, regardless of delivery, compared to the control groups. The means of delivery (IP versus IV) also yielded significant differences in ND. The incidence of mitochondrial dysmorphology and apoptosis were lower in groups receiving AST.

CONCLUSIONS

AST seems to suppress ND and has anti-apoptotic activity in the HIR mouse model.

摘要

目的

评估玻璃体内(IV)和腹腔内(IP)虾青素(AST)注射对高氧诱导视网膜病变(HIR)C57BL/6J 小鼠模型中新生血管形成(ND)、视网膜形态和细胞凋亡活性的影响。

设计

C57BL/6J 小鼠模型。

方法

两组 C57BL/6J 型小鼠(每组 6 只,其中一组接受 IV 无菌二甲基亚砜 [DMSO])作为阴性对照,置于室内空气中。HIR 组包括 36 只 C57BL/6J 型小鼠,从出生后第 7 天(PD)至第 12 天(PD)暴露于 75%±2%的氧气中。在 PD 12 时,这些小鼠随机分为 6 组(每组 6 只):2 个 HIR 对照组(其中一组接受 IV-DMSO)、2 个 IV-AST 组(10 和 100 µg/mL)和 2 个 IP-AST 组(0.5 和 5 mg/kg)。我们通过计数切片中的新生血管簇来测量 ND,并通过光镜和电子显微镜检查组织学、超微结构变化。使用末端脱氧核苷酸转移酶介导的缺口末端标记法检测细胞凋亡。

结果

阴性对照组未发现 ND。两种给药方式的高、低剂量 AST 组之间的 ND 水平无显著差异。然而,与对照组相比,AST 组(无论给药方式如何)的 ND 水平均显著降低。给药方式(IP 与 IV)在 ND 方面也有显著差异。接受 AST 治疗的组中线粒体形态异常和凋亡的发生率较低。

结论

AST 似乎能抑制 HIR 小鼠模型中的 ND,并具有抗凋亡活性。

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