Tian Ye, Xu Gang, Gao Hong, Xie Hong-Yan, Leng Yu-Lin, Fu Xiao-Xu, Xie Chun-Guang
TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Evid Based Complement Alternat Med. 2022 Sep 28;2022:6686931. doi: 10.1155/2022/6686931. eCollection 2022.
Disruption of the vascular immunological inflammatory microenvironment is linked to metabolic memory impairment. Even though it has been proven that the Shen-Qi compound (SQC) can efficiently halt metabolic memory and preserve vascular endothelial cells, extensive studies need to be done to investigate if it can also change the vascular immune-inflammatory microenvironment by regulating the immune system. This will help figure out the role of stopping metabolic memory.
After 4 weeks on a high-fat diet (HFD), GK rats were used to create a model for diabetic thoracic aortic problems. The effect and mechanisms of SQC on diabetic thoracic aortic complications were assessed by hematoxylin-eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), biochemical analysis, terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), reverse transcription, real-time polymerase chain reaction (RT-qPCR), immunofluorescence (IF), western blot, and luciferase reporter assays.
SQC treatment ameliorates the HFD-induced pathological symptoms as well as the HFD-induced increased concentrations of fasting blood glucose (FBG), fasting insulin (FINS), total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C) and decreased concentrations of high-density lipoprotein cholesterol (HDL-C). Besides, SQC counteracted the HFD-induced average fluorescence intensity of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), as well as the concentrations of endothelin-1 (ET-1) and monocyte chemoattractant protein-1 (MCP-1), while rescuing the HFD-induced concentrations of nitric oxide (NO) and nitric oxide synthetase (NOS). Also, SQC decreases apoptosis and oxidative stress in rats with diabetic thoracic aortic complications. In addition, SQC facilitated the polarization of macrophages, stimulated the activation of dendritic cells, and regulated the inflammatory milieu in rats with diabetic thoracic aortic complications. Furthermore, SQC also modulated the miR-223-3p/RBP-J/IRF8 axis in the macrophages of rats with diabetic thoracic aortic complications.
SQC ameliorated diabetic thoracic aortic complications through the regulation of apoptosis, oxidative stress, and inflammatory microenvironment mediating by the miR-223-3p/RBP-J/IRF8 axis.
血管免疫炎症微环境的破坏与代谢记忆受损有关。尽管已证实参芪复方（SQC）能有效阻止代谢记忆并保护血管内皮细胞，但仍需进行大量研究以探究其是否也能通过调节免疫系统来改变血管免疫炎症微环境。这将有助于明确阻止代谢记忆的作用。
高脂饮食（HFD）喂养4周后，使用GK大鼠建立糖尿病胸主动脉病变模型。通过苏木精-伊红（H&E）染色、酶联免疫吸附测定（ELISA）、生化分析、末端脱氧核苷酸转移酶脱氧尿苷三磷酸（dUTP）缺口末端标记（TUNEL）、逆转录、实时聚合酶链反应（RT-qPCR）、免疫荧光（IF）、蛋白质免疫印迹法和荧光素酶报告基因检测，评估SQC对糖尿病胸主动脉并发症的作用及机制。
SQC治疗改善了HFD诱导的病理症状以及HFD诱导的空腹血糖（FBG）、空腹胰岛素（FINS）、总胆固醇（TC）、甘油三酯（TGs）和低密度脂蛋白胆固醇（LDL-C）浓度升高，以及高密度脂蛋白胆固醇（HDL-C）浓度降低。此外，SQC抵消了HFD诱导的血管细胞黏附分子-1（VCAM-1）和细胞间黏附分子-1（ICAM-1）的平均荧光强度，以及内皮素-1（ET-1）和单核细胞趋化蛋白-1（MCP-1）的浓度，同时挽救了HFD诱导的一氧化氮（NO）和一氧化氮合酶（NOS）浓度。此外，SQC降低了糖尿病胸主动脉并发症大鼠的细胞凋亡和氧化应激。此外，SQC促进了巨噬细胞的极化，刺激了树突状细胞的活化，并调节了糖尿病胸主动脉并发症大鼠的炎症环境。此外，SQC还调节了糖尿病胸主动脉并发症大鼠巨噬细胞中的miR-223-3p/RBP-J/IRF8轴。
SQC通过调节由miR-223-3p/RBP-J/IRF8轴介导的细胞凋亡、氧化应激和炎症微环境，改善了糖尿病胸主动脉并发症。
