Liu Chun-Meng, Wang Jin-Yan, Gao Ming-Xue, Ding Shan, Zhang Fu-Wen
Eye School, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China.
Key Laboratory of Sichuan Province Ophthalmopathy Prevention & Cure and Visual Function Protection with TCM Laboratory, Chengdu, 610075, China.
Chin J Integr Med. 2025 Jun 10. doi: 10.1007/s11655-025-4131-3.
To investigate the inhibitory effects and underlying mechanisms of Qideng Mingmu Capsules (QD) on retinal neovascularization (RNV).
Seven-day-old C57BL/6J mice were assigned to the following groups: control, oxygen-induced retinopathy (OIR), low-, medium-, high-dose QD (225, 450, and 900 mg/g daily), and angiopoietin 1 (Ang1), 20 mice in each group. Except for the control group, an OIR model was induced by exposing mice to a hyperoxic environment for 5 d (postnatal days 7-12), followed by a normoxic environment for 5 d (postnatal days 12-17). From day 12, the treatment groups received QD orally or Ang1 via binocular intravitreal injection. On day 17, hematoxylin and eosin staining and fluorescein isothiocyanate-dextran staining were performed to evaluate RNV growth. Immunofluorescence staining, immunohistochemistry, and Western blotting were used to analyze the expressions of Ang/tyrosine kinase with immunoglobulin and epidermal growth factor homology domain-2 (Tie2) signaling pathway, hypoxia-inducible factor-1α (HIF-1α), and retinal vascular maturation markers. In addition, the effects of QD on the viability of rat retinal microvascular endothelial cells (rRMECs) was assessed.
QD significantly inhibited RNV formation, reduced RNV density, increased the expressions of Ang1, Tie2, and phosphorylated protein kinase B, and decreased the expression of Ang2 (P<0.05 or P<0.01). QD also enhanced retinal vascular pericyte coverage, reduced HIF-1α expression, and increased vascular endothelial cadherin levels (P<0.05 or P<0.01). Furthermore, no adverse effects were observed on the viability of rRMECs after QD intervention.
QD effectively inhibited RNV formation, promoted neovascular maturation and remodeling, and protected retinal function by modulating the Ang/Tie2 signaling pathway. Therefore, QD may serve as a promising therapeutic option for retinal neovascular diseases.
探讨芪灯明目胶囊（QD）对视网膜新生血管形成（RNV）的抑制作用及其潜在机制。
将7日龄C57BL/6J小鼠分为以下几组：对照组、氧诱导视网膜病变（OIR）组、低、中、高剂量QD组（分别为每日225、450和900 mg/g）以及血管生成素1（Ang1）组，每组20只小鼠。除对照组外，通过将小鼠置于高氧环境5天（出生后第7 - 12天），随后置于常氧环境5天（出生后第12 - 17天）诱导OIR模型。从第12天起，治疗组小鼠口服QD或通过双眼玻璃体内注射Ang1。在第17天，进行苏木精-伊红染色和异硫氰酸荧光素-葡聚糖染色以评估RNV生长。采用免疫荧光染色、免疫组织化学和蛋白质印迹法分析血管生成素/含免疫球蛋白和表皮生长因子同源结构域-2的酪氨酸激酶（Tie2）信号通路、缺氧诱导因子-1α（HIF-1α）以及视网膜血管成熟标志物的表达。此外，评估QD对大鼠视网膜微血管内皮细胞（rRMECs）活力的影响。
QD显著抑制RNV形成，降低RNV密度，增加Ang1、Tie2和磷酸化蛋白激酶B的表达，并降低Ang2的表达（P<0.05或P<0.01）。QD还增强了视网膜血管周细胞覆盖率，降低HIF-1α表达，并增加血管内皮钙黏蛋白水平（P<0.05或P<0.01）。此外，QD干预后未观察到对rRMECs活力的不良影响。
QD通过调节Ang/Tie2信号通路有效抑制RNV形成，促进新生血管成熟和重塑，并保护视网膜功能。因此，QD可能是视网膜新生血管疾病的一种有前景的治疗选择。
