Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; and.
J Cardiovasc Pharmacol. 2021 Feb 19;77(4):458-469. doi: 10.1097/FJC.0000000000000970.
Chronic stable angina (CSA) is caused by coronary atherosclerosis. The gut microbiota (GM) and their metabolite trimethylamine-N-oxide (TMAO) levels are associated with atherosclerosis. Danlou tablet (DLT) combined with Salvia miltiorrhiza ligustrazine (SML) injection has been used to treat CSA. This study aims to investigate how DLT combined with SML (DLT-SML) regulates serum lipids, inflammatory cytokines, GM community, and microbial metabolite in patients with CSA. In this study, 30 patients with CSA were enrolled in the DLT-SML group, and 10 healthy volunteers were included in the healthy control group. The patients in the DLT-SML group were subdivided as the normal total cholesterol (TC) group and high-TC group according to their serum TC level before treatment. Blood samples were collected to investigate the (1) lipid content, including triglyceride (TG), TC, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, (2) fasting blood glucose (Glu), (3) inflammatory cytokines, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α), and (4) gut-derived metabolite, including lipopolysaccharides and TMAO level. GM composition was analyzed by sequencing 16S rRNA of fecal samples. Results showed that DLT-SML significantly decreased serum TG, TC, low-density lipoprotein cholesterol, IL-1β, TNF-α, and TMAO levels of patients with CSA. DLT-SML increased the abundance of Firmicutes and decreased Proteobacteria, which were significantly lower or higher in patients with CSA, respectively, compared with the healthy control group. In particular, DLT-SML increased the microbial diversity and decreased Firmicutes/Bacteroidetes ratio of patients with high-TC. The abundance of Sarcina, Anaerostipes, Streptococcus, Weissella, and Erysipelatoclostridium was decreased, whereas Romboutsia, Faecalibacterium, and Subdoligranulum were increased by DLT-SML treatment in patients with CSA. These findings indicated that DLT-SML improved patients with CSA by ameliorating dyslipidemia profile, decreasing the circulating inflammatory cytokines, and regulating the GM composition and their metabolites.
慢性稳定性心绞痛（CSA）是由冠状动脉粥样硬化引起的。肠道微生物群（GM）及其代谢产物三甲胺 N-氧化物（TMAO）水平与动脉粥样硬化有关。丹络片（DLT）联合丹参川芎嗪注射液已用于治疗 CSA。本研究旨在探讨 DLT 联合丹参川芎嗪（DLT-SML）如何调节 CSA 患者的血清脂质、炎症细胞因子、GM 群落和微生物代谢物。
在这项研究中，30 名 CSA 患者被纳入 DLT-SML 组，10 名健康志愿者被纳入健康对照组。根据治疗前血清 TC 水平，DLT-SML 组患者进一步分为正常总胆固醇（TC）组和高 TC 组。采集血样以研究：（1）血脂含量，包括甘油三酯（TG）、TC、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇，（2）空腹血糖（Glu），（3）炎症细胞因子，包括白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）和肿瘤坏死因子-α（TNF-α），以及（4）肠道衍生代谢物，包括脂多糖和 TMAO 水平。通过粪便样本 16S rRNA 测序分析 GM 组成。
结果显示，DLT-SML 可显著降低 CSA 患者的血清 TG、TC、低密度脂蛋白胆固醇、IL-1β、TNF-α和 TMAO 水平。与健康对照组相比，DLT-SML 增加了厚壁菌门的丰度，降低了变形菌门的丰度，分别是 CSA 患者中丰度较低和较高的菌门。特别是，DLT-SML 增加了高 TC 患者的微生物多样性并降低了厚壁菌门/拟杆菌门的比例。DLT-SML 治疗后，CSA 患者的 Sarcina、Anaerostipes、Streptococcus、Weissella 和 Erysipelatoclostridium 的丰度降低，而 Romboutsia、Faecalibacterium 和 Subdoligranulum 的丰度增加。
这些发现表明，DLT-SML 通过改善血脂谱、降低循环炎症细胞因子以及调节 GM 组成及其代谢物来改善 CSA 患者的病情。
