Zhu Suhua, Zhang Man, Qu Zhen, Xu Shengqiu, Peng Jie, Jiang Fanjing
Department of Pharmacy Xuzhou No.1 People's Hospital Xuzhou Jiangsu China.
Department of Pharmacy Yancheng No.1 People's Hospital Yancheng Jiangsu China.
J Cell Commun Signal. 2025 Feb 19;19(1):e12059. doi: 10.1002/ccs3.12059. eCollection 2025 Mar.
Diabetic retinopathy (DR), as the main ophthalmic complication of diabetes mellitus, is a major eye disorder contributing to blindness. Oxidative stress and inflammation in retinal Müller cells participate in the pathogenesis of DR. This work aims to study the biological role of moscatilin in the progression of DR and the underlying mechanism. High glucose (HG)-stimulated mouse primary retinal Müller cells and high-fat diet + streptozotocin (STZ)-induced DR mouse models were constructed as in vitro and in vivo models, respectively. The effects of moscatilin treatment on oxidative stress and inflammation in HG-stimulated Müller cells and DR mice were evaluated by detecting intracellular reactive oxygen species production, malondialdehyde levels, superoxide dismutase and catalase activities, glutathione/oxidized glutathione ratio, as well as proinflammatory cytokine levels through CM-HDCFDA staining, commercial kits, and enzyme-linked immunosorbent assay. Dual immunofluorescence staining of glial fibrillary acidic protein and vimentin was used to evaluate the development of Müller cells in mouse retinas. The activity of p38 mitogen-activated protein kinase (MAPK)/c-Jun N-terminal kinase (JNK) and nuclear factor kappa-B (NF-κB) signaling pathway was assessed through western blotting and immunofluorescence staining. Moscatilin pretreatment prevented HG-induced decrease in Müller cell viability. Moscatilin mitigated oxidative stress, inflammation, and extracellular matrix remodeling in HG-stimulated Müller cells and DR mice. Mechanically, moscatilin reduced the levels of receptor for advanced glycation end products, phosphorylated I-kappa-B-alpha, p-p65 NF-κB, p-p38 MAPK, and p-JNK in both HG-stimulated Müller cells and DR mice. Moscatilin plays an antioxidant and anti-inflammatory role in DR by inhibiting the p38 MAPK/JNK and NF-κB signaling pathways.
糖尿病视网膜病变（DR）作为糖尿病的主要眼部并发症，是导致失明的一种主要眼部疾病。视网膜Müller细胞中的氧化应激和炎症参与了DR的发病机制。本研究旨在探讨桑色素在DR进展中的生物学作用及其潜在机制。分别构建了高糖（HG）刺激的小鼠原代视网膜Müller细胞和高脂饮食+链脲佐菌素（STZ）诱导的DR小鼠模型作为体外和体内模型。通过CM-HDCFDA染色、商业试剂盒和酶联免疫吸附测定法检测细胞内活性氧生成、丙二醛水平、超氧化物歧化酶和过氧化氢酶活性、谷胱甘肽/氧化型谷胱甘肽比值以及促炎细胞因子水平，评估桑色素处理对HG刺激的Müller细胞和DR小鼠氧化应激和炎症的影响。采用胶质纤维酸性蛋白和波形蛋白的双重免疫荧光染色评估小鼠视网膜中Müller细胞的发育情况。通过蛋白质免疫印迹法和免疫荧光染色评估p38丝裂原活化蛋白激酶（MAPK）/c-Jun氨基末端激酶（JNK）和核因子κB（NF-κB）信号通路的活性。桑色素预处理可防止HG诱导的Müller细胞活力下降。桑色素减轻了HG刺激的Müller细胞和DR小鼠的氧化应激、炎症和细胞外基质重塑。机制上，桑色素降低了HG刺激的Müller细胞和DR小鼠中晚期糖基化终末产物受体、磷酸化I-κB-α、p-p65 NF-κB、p-p38 MAPK和p-JNK的水平。桑色素通过抑制p38 MAPK/JNK和NF-κB信号通路在DR中发挥抗氧化和抗炎作用。
