Gong Chen-Yuan, Yu Zeng-Yang, Lu Bin, Yang Li, Sheng Yu-Chen, Fan Yuan-Min, Ji Li-Li, Wang Zheng-Tao
The MOE Key Laboratory for Standardization of Chinese Medicines and Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Center for Drug Safety Evaluation and Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Vascul Pharmacol. 2014 Sep;62(3):134-42. doi: 10.1016/j.vph.2014.04.007. Epub 2014 May 16.
Diabetic retinopathy (DR) is the most common and serious complication of diabetes mellitus (DM). The present study investigates the amelioration of ethanol extract of Dendrobium chrysotoxum Lindl (DC) on streptozotocin (STZ)-induced DR and its engaged mechanism. Retinal immunofluorescence staining with cluster of differentiation 31 (CD31) demonstrated that DC (30-300 mg/kg) decreased the increased retinal vessels in STZ-induced diabetic rats. Retinal histopathological observation also showed that retinal vessels were decreased in DC-treated diabetic rats. DC decreased the increased retinal mRNA expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) in diabetic rats, and DC also decreased the elevated serum VEGF level. Immunohistochemical staining further evidenced that DC decreased VEGF and VEGFR2 expression in retinas. Retinal mRNA expression of matrix metalloproteinase (MMP) 2/9 was decreased in DC (300 mg/kg)-treated diabetic rats. Serum levels of MMP 2/9, basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) A/B, insulin-like growth factor 1 (IGF-1), interleukin 1β (IL-1β), and IL-6 were all decreased in DC-treated diabetic rats. In addition, DC decreased the increased phosphorylation of p65 and the increased expression of intercellular adhesion molecule-1 (ICAM-1). In conclusion, DC can alleviate retinal angiogenesis during the process of DR via inhibiting the expression of VEGF/VEGFR2, and some other pro-angiogenic factors such as MMP 2/9, PDGF A/B, bFGF, IGF-1. In addition, DC can also ameliorate retinal inflammation via inhibiting NFκB signaling pathway.
糖尿病视网膜病变(DR)是糖尿病(DM)最常见且最严重的并发症。本研究探讨了金钗石斛乙醇提取物(DC)对链脲佐菌素(STZ)诱导的DR的改善作用及其作用机制。用分化簇31(CD31)进行视网膜免疫荧光染色表明,DC(30 - 300mg/kg)可减少STZ诱导的糖尿病大鼠视网膜血管的增多。视网膜组织病理学观察也显示,DC处理的糖尿病大鼠视网膜血管减少。DC降低了糖尿病大鼠视网膜中血管内皮生长因子(VEGF)和VEGF受体2(VEGFR2)mRNA表达的增加,并且DC还降低了血清VEGF水平的升高。免疫组织化学染色进一步证明DC降低了视网膜中VEGF和VEGFR2的表达。在DC(300mg/kg)处理的糖尿病大鼠中,基质金属蛋白酶(MMP)2/9的视网膜mRNA表达降低。DC处理的糖尿病大鼠血清中MMP 2/9、碱性成纤维细胞生长因子(bFGF)、血小板衍生生长因子(PDGF)A/B、胰岛素样生长因子1(IGF - 1)、白细胞介素1β(IL - 1β)和IL - 6水平均降低。此外,DC降低了p65磷酸化的增加以及细胞间黏附分子1(ICAM - 1)表达的增加。总之,DC可通过抑制VEGF/VEGFR2以及其他一些促血管生成因子如MMP 2/9、PDGF A/B、bFGF、IGF - 1的表达来减轻DR过程中的视网膜血管生成。此外,DC还可通过抑制NFκB信号通路改善视网膜炎症。