炎症体
发病机制
肠道菌群
肾脏疾病
医学
肾功能
心功能曲线
肾
内科学
药理学
心肌保护
内分泌学
炎症
免疫学
缺血
心力衰竭
作者
Tong‐Tong Liu,Xiaoguang Lu,Wenya Gao,Yuanyuan Zhai,Han Li,Shangheng Li,Liping Yang,Fang Ma,Yongli Zhan,Huimin Mao
标识
DOI:10.1016/j.biopha.2022.113159
摘要
The pathogenesis and treatment of cardiovascular disease mediated by chronic kidney disease (CKD) are key research questions. Specifically, the mechanisms underlying the cardiorenal protective effect of Yiqi-Huoxue-Jiangzhuo formula (YHJF), a traditional Chinese herbal medicine, have not yet been clarified.A classical CKD mouse model was constructed by 5/6 nephrectomy (Nx) to study the effects of YHJF intervention on 5/6 Nx mice cardiorenal function, gut microbial composition, gut-derived metabolites, and NLRP3 inflammasome pathways.YHJF improved cardiac dysfunction and reversed left ventricular hypertrophy, myocardial hypertrophy, and interstitial fibrosis in 5/6 Nx mice. In addition, YHJF inhibited activation of the NLRP3 inflammasome and downregulated the expression of TNF-α and IL-1β both in the heart and serum; reconstitution of the intestinal flora imbalance was also found in 5/6 Nx mice treated with YHJF. Spearman's correlation and redundancy analyses showed that changes in the intestinal flora of 5/6 Nx mice were related to clinical phenotype and serum inflammatory levels.Treatment with YHJF effectively protected the heart function of 5/6 Nx mice; this effect was attributed to inhibition of NLRP3 inflammasome activation and regulation of intestinal microbial composition and derived metabolites. YHJF has potential for improving intestinal flora imbalance and gut-derived toxin accumulation in patients with CKD, thereby preventing cardiovascular complications.
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