Yang Bing, Ma Guobin, Liu Yang
Department of Endocrinology and Metabolism, 3201 Hospital, Xi'an Jiaotong University Health Science Center, Hanzhong, Shaanxi, China (mainland).
Med Sci Monit. 2020 Oct 4;26:e925087. doi: 10.12659/MSM.925087.
BACKGROUND Diabetic retinopathy (DR) is one of the major causes of vision impairment. Z-ligustilide (3-butylidene-4,5-dihydrophthalide; Z-LIG) is an important volatile oil from the Chinese herb Angelica sinensis (Oliv.) Diels. It has been extensively studied and reportedly has anti-inflammatory, antioxidant, antitumor, analgesic, vasodilatory, and neuroprotective effects. Its effects on DR, however, remain obscure. In this study, we attempted to explore the protective effects of Z-LIG on retinal dysfunction and the potential underlying mechanisms. MATERIAL AND METHODS A diabetic rat model was constructed with streptozotocin injection. Three study groups were constituted: control (CON), diabetic model (DM), and DM+Z-LIG. The DM+Z-LIG group was injected intraperitoneally with 10 mg/kg of Z-LIG. The other groups received the same volume of 3% solution of polysorbate 80. After a 12-week intervention, a series of assessments were performed, including tests for retinal function, morphology, and molecular biology. RESULTS Z-LIG treatment significantly elevated b-wave and OPs2-wave amplitude and thickened the inner layer of the nucleus of the retina, and the outer plexiform and nuclear layers (INL+OPL+ONL). Moreover, the rate of apoptosis and expression of bcl-2- associated X protein (BAX) and cleaved-Caspase-3 were clearly reduced, and the expression of bcl-2 was raised by Z-LIG in retinas of diabetic mice. In addition, the levels of retinal proinflammatory cytokines interleukin-1 and tumor necrosis factor-alpha were downregulated by Z-LIG. Furthermore, Z-LIG inhibited expression of vascular endothelial growth factor-alpha (VEGF-alpha) at the mRNA and protein levels. CONCLUSIONS Z-LIG can inhibit inflammatory response and cell apoptosis in retinas of diabetic rats by repressing the VEGF-alpha pathway. Therefore, it may serve as a potential therapeutic agent for DR.
背景 糖尿病性视网膜病变（DR）是视力损害的主要原因之一。Z-藁本内酯（3-亚丁基-4,5-二氢苯酞；Z-LIG）是中药当归中的一种重要挥发油。它已被广泛研究，据报道具有抗炎、抗氧化、抗肿瘤、镇痛、血管舒张和神经保护作用。然而，其对DR的影响仍不清楚。在本研究中，我们试图探讨Z-LIG对视网膜功能障碍的保护作用及其潜在的机制。
材料与方法 通过注射链脲佐菌素构建糖尿病大鼠模型。组成三个研究组：对照组（CON）、糖尿病模型组（DM）和DM+Z-LIG组。DM+Z-LIG组腹腔注射10mg/kg的Z-LIG。其他组接受相同体积的3%聚山梨酯80溶液。经过12周的干预后，进行了一系列评估，包括视网膜功能、形态学和分子生物学检测。
结果 Z-LIG治疗显著提高了b波和OPs2波振幅，并使视网膜内核层、外网状层和核层（INL+OPL+ONL）增厚。此外，Z-LIG明显降低了糖尿病小鼠视网膜中凋亡率以及bcl-2相关X蛋白（BAX）和裂解的半胱天冬酶-3的表达，并提高了bcl-2的表达。此外，Z-LIG下调了视网膜促炎细胞因子白细胞介素-1和肿瘤坏死因子-α的水平。此外，Z-LIG在mRNA和蛋白质水平上抑制血管内皮生长因子-α（VEGF-α）的表达。
结论 Z-LIG可通过抑制VEGF-α途径抑制糖尿病大鼠视网膜的炎症反应和细胞凋亡。因此，它可能成为DR的一种潜在治疗药物。
