Ji Wenyan, Jiang Ting, Sun Zheng, Teng Fei, Ma Chenchen, Huang Shi, Yan Suhua
School of Medicine, Shandong University, Jinan, China.
Department of Cardiology, Qingdao Municipal Hospital of Traditional Chinese Medicine (Qingdao Hiser Medical Group), Qingdao, China.
Front Pharmacol. 2020 Oct 15;11:546589. doi: 10.3389/fphar.2020.546589. eCollection 2020.
Accumulating evidence indicated that gut microbiota-targeted therapy is a promising strategy to treat Cardiovascular Disease (CVD). Traditional Chinese Medicine (TCM) has been used in CVD treatments for over 2,000 years which is believed to result from the modulation of gut microbiota, yet the underlying mechanism remains elusive. According to the theoretical system of TCM, we developed an innovative formula of TCM named "TongMai ZhuYu (TMZY)" on top of one classic Chinese herbal formula ["XueFu ZhuYu (XFZY)"], which can more effectively alleviate CVD in the clinical practice. Here, we first systematically assessed the pharmacological effects of TMZY, XFZY, and atorvastatin on atherosclerosis (AS) induced by high-fat diet (HFD) in rats. TMZY typically outperformed others in alleviating AS rats by characterization of pathological morphology, immunohistochemistry, inflammatory cytokines. Remarkably, combining this modified TCM formula (TMZY) with atorvastatin can further help the alleviation of AS in rats by suppressing immune and inflammatory responses. Furthermore, to test whether TMZY alleviated AS symptoms by altering gut microbial compositions (dysbiosis), we employed 16S amplicon sequencing to investigate gut microbiota changes in the AS mice induced by high choline diet (HCD) using both TMZY and XFZY under antibiotic-treated and untreated conditions. TCM formulas induced consistent and remarkable changes in the phenotypes and microbiota in the HCD mice. TMZY modulated more changes in the gut microbiota to improve diseased phenotypes than XFZY. Notably, the TMZY-intervention effect on CVD in mice attenuated after the suppression of gut microbial activity by antibiotics. Collectively, we demonstrated that TCM herbals could effectively modulate the gut microbiota as a mechanism for altering the pathogenesis of cardiovascular disorders in mice/rats.
越来越多的证据表明，针对肠道微生物群的疗法是治疗心血管疾病（CVD）的一种有前景的策略。中药已用于CVD治疗两千多年，人们认为这是由于其对肠道微生物群的调节作用，但潜在机制仍不清楚。根据中医理论体系，我们在一个经典中药方剂["血府逐瘀（XFZY）"]的基础上，开发了一种名为"通脉逐瘀（TMZY）"的创新中药方剂，在临床实践中能更有效地缓解CVD。在此，我们首先系统评估了TMZY、XFZY和阿托伐他汀对高脂饮食（HFD）诱导的大鼠动脉粥样硬化（AS）的药理作用。通过病理形态学、免疫组织化学、炎性细胞因子等特征分析，TMZY在缓解AS大鼠方面通常优于其他药物。值得注意的是，将这种改良的中药方剂（TMZY）与阿托伐他汀联合使用，可以通过抑制免疫和炎症反应进一步帮助缓解大鼠的AS。此外，为了测试TMZY是否通过改变肠道微生物组成（失调）来缓解AS症状，我们采用16S扩增子测序技术，研究在抗生素处理和未处理条件下，TMZY和XFZY对高胆碱饮食（HCD）诱导的AS小鼠肠道微生物群变化的影响。中药方剂在HCD小鼠的表型和微生物群中引起了一致且显著的变化。与XFZY相比，TMZY对肠道微生物群的调节作用更大，能改善疾病表型。值得注意的是，抗生素抑制肠道微生物活性后，TMZY对小鼠CVD的干预作用减弱。总的来说，我们证明了中药可以有效调节肠道微生物群，作为改变小鼠/大鼠心血管疾病发病机制的一种机制。
