College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin 150030, China.
Molecules. 2017 Sep 25;22(10):1610. doi: 10.3390/molecules22101610.
Cadmium (Cd) is a known environmental pollutant that is associated with inflammation, oxidative stress, and cell apoptosis. Astragalus polysaccharide (APS) is a major component of , a vital qi-reinforcing herb medicine with favorable immuneregulation properties. To study the effect of APS on the inhibition of the cadmium-induced injury of peripheral blood lymphocytes (PBLs) in chickens through the signaling pathway, PLBs acquired from 15-day-old chickens were divided into control group, Cd group, APS + Cd group, anti-MDA5 mAb + Cd group, BAY 11-7082 (a nuclear factor kappa-light chain-enhancer of activated B cells [] inhibitor) +Cd group, APS group, anti-MDA5 mAb group, and BAY 11-7082 group. The transcription levels of melanoma differentiation-associated gene 5 (), interferon promoter-stimulating factor 1 (), , and inflammatory factors tumor necrosis factor ()-α, interleukin ()-1β, and were measured by quantitative real-time PCR. MDA5 protein expression was measured by western blotting. Levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) were measured by corresponding antioxidant kit. The morphological change of PBLs was measured by transmission electron microscopy. The results showed that Cd significantly increased the expression of , , , and their downstream cytokines, and , in PLBs. In addition, a high level of MDA was observed in the Cd treatment group; the activities of GSH-Px and SOD were significantly lower in the Cd treatment group than those in controls ( < 0.05). Ultrastructural changes of PBLs showed that Cd promoted autophagy, apoptosis, and necrosis in PBLs. However, APS can efficiently improve Cd-induced cell damage by decreasing the activation of the signaling pathway. The effect is consistent with that of anti-MDA5 mAb or/and BAY. The results indicated that APS inhibited Cd-induced cytotoxicity through the regulation of MDA5/NF-κB signaling.
镉 (Cd) 是一种已知的环境污染物，与炎症、氧化应激和细胞凋亡有关。黄芪多糖 (APS) 是 的主要成分，是一种具有良好免疫调节特性的重要补气草药。为了研究 APS 通过 信号通路对抑制鸡外周血淋巴细胞 (PBL) 中镉诱导损伤的作用，从 15 日龄鸡中分离出 PBL，分为对照组、Cd 组、APS+Cd 组、抗 MDA5 mAb+Cd 组、BAY 11-7082（核因子 κB 轻链增强子激活 B 细胞 [] 抑制剂）+Cd 组、APS 组、抗 MDA5 mAb 组和 BAY 11-7082 组。采用实时定量 PCR 法测定黑色素瘤分化相关基因 5 ()、干扰素启动子刺激因子 1 ()、()、炎症因子肿瘤坏死因子 ()-α、白细胞介素 ()-1β和 的转录水平。用 Western blot 法测定 MDA5 蛋白表达。用相应的抗氧化试剂盒测定丙二醛 (MDA)、谷胱甘肽过氧化物酶 (GSH-Px) 和超氧化物歧化酶 (SOD) 的水平。用透射电子显微镜观察 PBL 的形态变化。结果表明，Cd 显著增加了 PLBs 中 、 、 及其下游细胞因子 、 和 的表达。此外，在 Cd 处理组中观察到 MDA 水平升高；与对照组相比，Cd 处理组 GSH-Px 和 SOD 的活性显著降低 ( < 0.05)。PBL 的超微结构变化显示，Cd 促进了 PBL 中的自噬、凋亡和坏死。然而，APS 通过降低 信号通路的激活，有效地改善了 Cd 诱导的细胞损伤。这种作用与抗 MDA5 mAb 或/和 BAY 一致。结果表明，APS 通过调节 MDA5/NF-κB 信号抑制 Cd 诱导的细胞毒性。
