富含生育三烯酚的馏分可降低链脲佐菌素诱导糖尿病大鼠的视网膜炎症和血管生成。
Tocotrienol-rich fraction reduces retinal inflammation and angiogenesis in rats with streptozotocin-induced diabetes.
机构信息
Department of Pharmacology, Faculty of Medicine, Manipal University College Malaysia (MUCM), Bukit Baru, 75150, Melaka, Malaysia.
Centre for Neuroscience Research (NeuRon), Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, 47000, Sungai Buloh, Selangor, Malaysia.
出版信息
BMC Complement Med Ther. 2023 Jun 2;23(1):179. doi: 10.1186/s12906-023-04005-9.
BACKGROUND
Diabetic retinopathy (DR) is the second commonest microvascular complication of diabetes mellitus. It is characterized by chronic inflammation and angiogenesis. Palm oil-derived tocotrienol-rich fraction (TRF), a substance with anti-inflammatory and anti-angiogenic properties, may provide protection against DR development. Therefore, in this study, we investigated the effect of TRF on retinal vascular and morphological changes in diabetic rats. The effects of TRF on the retinal expression of inflammatory and angiogenic markers were also studied in the streptozotocin (STZ)-induced diabetic rats.
METHODS
Male Sprague Dawley rats weighing 200-250 g were grouped into normal rats (N) and diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (55 mg/kg body weight) whereas N similarly received citrate buffer. STZ-injected rats with blood glucose of more than 20 mmol/L were considered diabetic and were divided into vehicle-treated (DV) and TRF-treated (DT) groups. N and DV received vehicle, whereas DT received TRF (100 mg/kg body weight) via oral gavage once daily for 12 weeks. Fundus images were captured at week 0 (baseline), week 6 and week 12 post-STZ induction to estimate vascular diameters. At the end of experimental period, rats were euthanized, and retinal tissues were collected for morphometric analysis and measurement of NFκB, phospho-NFκB (Ser536), HIF-1α using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). Retinal inflammatory and angiogenic cytokines expression were measured by ELISA and real-time quantitative PCR.
RESULTS
TRF preserved the retinal layer thickness (GCL, IPL, INL and OR; p < 0.05) and retinal venous diameter (p < 0.001). TRF also lowered the retinal NFκB activation (p < 0.05) as well as expressions of IL-1β, IL-6, TNF-α, IFN-γ, iNOS and MCP-1 (p < 0.05) compared to vehicle-treated diabetic rats. Moreover, TRF also reduced retinal expression of VEGF (p < 0.001), IGF-1 (p < 0.001) and HIF-1α (p < 0.05) compared to vehicle-treated rats with diabetes.
CONCLUSION
Oral TRF provided protection against retinal inflammation and angiogenesis in rats with STZ-induced diabetes by suppressing the expression of the markers of retinal inflammation and angiogenesis.
背景
糖尿病视网膜病变（DR）是糖尿病最常见的微血管并发症之一。它的特征是慢性炎症和血管生成。源于棕榈油的生育三烯酚（TRF）是一种具有抗炎和抗血管生成特性的物质，可能对 DR 的发展有保护作用。因此，在这项研究中，我们研究了 TRF 对糖尿病大鼠视网膜血管和形态变化的影响。还研究了 TRF 对链脲佐菌素（STZ）诱导的糖尿病大鼠视网膜炎症和血管生成标志物表达的影响。
方法
雄性 Sprague Dawley 大鼠体重 200-250g 分为正常大鼠（N）和糖尿病大鼠。通过腹腔注射链脲佐菌素（55mg/kg 体重）诱导糖尿病，而 N 同样给予柠檬酸盐缓冲液。血糖超过 20mmol/L 的 STZ 注射大鼠被认为患有糖尿病，并分为 vehicle-treated（DV）和 TRF-treated（DT）组。N 和 DV 给予 vehicle，而 DT 给予 TRF（100mg/kg 体重）通过口服灌胃每天一次，共 12 周。在 STZ 诱导后第 0 周（基线）、第 6 周和第 12 周拍摄眼底图像，以估计血管直径。在实验期末，处死大鼠，收集视网膜组织进行形态计量分析，并使用免疫组织化学（IHC）和酶联免疫吸附测定（ELISA）测量 NFκB、磷酸化 NFκB（Ser536）、HIF-1α。通过 ELISA 和实时定量 PCR 测量视网膜炎症和血管生成细胞因子的表达。
结果
TRF 保存了视网膜层厚度（GCL、IPL、INL 和 OR；p<0.05）和视网膜静脉直径（p<0.001）。与 vehicle 治疗的糖尿病大鼠相比，TRF 还降低了视网膜 NFκB 激活（p<0.05）以及 IL-1β、IL-6、TNF-α、IFN-γ、iNOS 和 MCP-1 的表达（p<0.05）。此外，与 vehicle 治疗的糖尿病大鼠相比，TRF 还降低了视网膜中 VEGF（p<0.001）、IGF-1（p<0.001）和 HIF-1α（p<0.05）的表达。
结论
口服 TRF 通过抑制视网膜炎症和血管生成标志物的表达，为 STZ 诱导的糖尿病大鼠提供了对视网膜炎症和血管生成的保护。
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