Shang Luorui, Liu Yuhan, Li Jinxiao, Pan Guangtao, Zhou Fangyuan, Yang Shenglan
Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Pharmacol. 2021 Dec 20;12:724511. doi: 10.3389/fphar.2021.724511. eCollection 2021.
Emodin is an anthraquinone extracted from Polygonum multiflorum, which has potential anti-inflammatory and anti-oxidative stress effects. However, the possible protective mechanism of emodin is unclear. The purpose of this study was to investigate the protective mechanism of emodin against cecal ligation and puncture and LPS-induced intestinal mucosal barrier injury through the VDR/ Nrf2 /HO-1 signaling pathway. We established a mouse model of sepsis by cecal ligation and puncture (CLP), and stimulated normal intestinal epithelial cells with lipopolysaccharide (LPS). VDR in cellswas down-regulated by small interfering ribonucleic acid (siRNA) technology.Mice were perfused with VDR antagonists ZK168281 to reduce VDR expression and mRNA and protein levels of VDR and downstream molecules were detected in cells and tissue. Inflammation markers (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)) and oxidative stress markers (superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH)) were measured in serum and intestinal tissueby enzym-linked immunosorbent assay. The expression of VDR in intestinal tissue was detected by immunofluorescence. Histopathological changes were assessed by hematoxylin and eosin staining. In NCM460 cells and animal models, emodin increased mRNA and protein expression of VDR and its downstream molecules. In addition, emodin could inhibit the expressions of TNF-α, IL-6 and MDA in serum and tissue, and increase the levels of SOD and GSH. The protective effect of emodin was confirmed in NCM460 cells and mice, where VDR was suppressed. In addition, emodin could alleviate the histopathological damage of intestinal mucosal barrier caused by cecal ligation and puncture. Emodin has a good protective effect against sepsis related intestinal mucosal barrier injury, possibly through the VDR/ Nrf2 /HO-1 pathway.
大黄素是从何首乌中提取的一种蒽醌，具有潜在的抗炎和抗氧化应激作用。然而，大黄素可能的保护机制尚不清楚。本研究旨在探讨大黄素通过维生素D受体（VDR）/核因子E2相关因子2（Nrf2）/血红素加氧酶-1（HO-1）信号通路对盲肠结扎穿刺及脂多糖（LPS）诱导的肠黏膜屏障损伤的保护机制。我们通过盲肠结扎穿刺（CLP）建立了脓毒症小鼠模型，并用脂多糖（LPS）刺激正常肠上皮细胞。采用小干扰核糖核酸（siRNA）技术下调细胞中的VDR。给小鼠灌注VDR拮抗剂ZK168281以降低VDR表达，并检测细胞和组织中VDR及其下游分子的mRNA和蛋白水平。通过酶联免疫吸附测定法检测血清和肠组织中的炎症标志物（肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6））和氧化应激标志物（超氧化物歧化酶（SOD）、丙二醛（MDA）和谷胱甘肽（GSH））。通过免疫荧光检测肠组织中VDR的表达。通过苏木精和伊红染色评估组织病理学变化。在NCM460细胞和动物模型中，大黄素增加了VDR及其下游分子的mRNA和蛋白表达。此外，大黄素可抑制血清和组织中TNF-α、IL-6和MDA的表达，并提高SOD和GSH水平。在VDR被抑制的NCM460细胞和小鼠中证实了大黄素的保护作用。此外，大黄素可减轻盲肠结扎穿刺引起的肠黏膜屏障组织病理学损伤。大黄素对脓毒症相关肠黏膜屏障损伤具有良好的保护作用，可能是通过VDR/Nrf2/HO-1通路实现的。
