Academy of Chinese Medicine & Institute of Comparative Medicine, Zhejiang Chinese Medical University, Hangzhou, China.
Department of Experimental Animals, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China.
J Immunol Res. 2022 Jul 28;2022:7128230. doi: 10.1155/2022/7128230. eCollection 2022.
Coronary atherosclerosis (CA) is a chronic and evolving inflammatory disease characterized by the build-up of atherosclerotic plaque in the wall of coronary arteries. Guanxinning tablet (GXNT) is a novel Chinese medicine formula, which has been clinically used to treat coronary heart disease for many years. However, the potential mechanism for treating CA remains unclear. Thus, the study was aimed at investigating the therapeutic effect of GXNT on CA and further explore the underlying mechanisms from the perspective of gut microbiota. Following the establishment of a CA model in Tibetan minipigs, GXNT was orally administrated. We simultaneously detected blood lipid levels, observed ventricular function using ultrasound examination, measured platelet aggregation, and checked changes in inflammatory factors, oxidative stress factors, and vascular endothelial injury-related indexes applying ELISA assays. Histopathological changes of coronary artery tissue were subsequently evaluated using Sudan IV staining, HE staining, Oil red "O" staining, and immunohistochemistry assays. Finally, alterations of the gut microbiota and microbial metabolites were detected using metagenomic sequencing and targeted metabolomics, respectively. The results have suggested that GXNT could regulate dyslipidemia, improve heart function, and inhibit the levels of ox-LDL, CRP, TNF-, IL-1, SOD, MDA, vWF, and ET-1, as well as platelet aggregation. Additionally, histopathological findings revealed that GXNT could reduce lipid deposition, alleviate AS lesions, and restrain the expressions of NF-B, TNF-, and MMP-9. Furthermore, the composition of the gut microbiota was altered. Specifically, GXNT could upregulate the relative abundance of and and downregulate the abundance of , , and . As for microbial metabolites, GXNT could increase fecal propionic acid, butyric acid, and LCA-3S and decrease fecal TMA-related metabolites, CDCA, and serum TMAO. In sum, the results showed that GXNT had a satisfactory anti-CA effect, and the mechanism was closely associated with modulating gut microbiota and related metabolites.
冠状动脉粥样硬化（CA）是一种慢性进行性炎症性疾病，其特征是冠状动脉壁中动脉粥样硬化斑块的形成。冠心宁片（GXNT）是一种新型中药配方，临床上多年来一直用于治疗冠心病。然而，其治疗 CA 的潜在机制尚不清楚。因此，本研究旨在探讨 GXNT 对 CA 的治疗作用，并从肠道微生物群的角度进一步探讨其潜在机制。在建立藏猪 CA 模型后，通过口服给予 GXNT。我们同时检测了血脂水平，使用超声检查观察心室功能，测量血小板聚集，并通过 ELISA 检测炎症因子、氧化应激因子和血管内皮损伤相关指标的变化。随后，通过苏丹 IV 染色、HE 染色、油红“O”染色和免疫组织化学染色评估冠状动脉组织的组织病理学变化。最后，分别通过宏基因组测序和靶向代谢组学检测肠道微生物群和微生物代谢物的变化。结果表明，GXNT 可调节血脂异常，改善心功能，降低 ox-LDL、CRP、TNF-、IL-1、SOD、MDA、vWF 和 ET-1 水平及血小板聚集。此外，组织病理学发现 GXNT 可减少脂质沉积，减轻 AS 病变，并抑制 NF-B、TNF-和 MMP-9 的表达。此外，肠道微生物群的组成发生了改变。具体而言，GXNT 可上调相对丰度和，并下调的丰度。至于微生物代谢物，GXNT 可增加粪便丙酸、丁酸和 LCA-3S 的含量，降低粪便 TMA 相关代谢物、CDCA 和血清 TMAO 的含量。总之，结果表明 GXNT 具有良好的抗 CA 作用，其机制与调节肠道微生物群及其相关代谢物密切相关。
