Abstract：
Cardiac tissue remodeling is characterized by altered heart tissue architecture and dysfunction, leading to heart failure. Sustained activation of the renin-angiotensin-aldosterone system (RAAS) greatly promotes the development of myocardial remodeling. Angiotensin II (Ang II), which is the major component of RAAS, can directly lead to cardiac remodeling by inducing an inflammatory response. Schisandrin B (Sch B), the active component extracted from the fruit of Schisandra chinensis (Turcz.) Baill has been shown to exhibit anti-inflammatory activity through its ability to target TLR4 and its adaptor protein, MyD88. In this study, we explored whether Sch B alleviates Ang II-induced myocardial inflammation and remodeling via targeting MyD88. Sch B significantly suppressed Ang II-induced inflammation as well as increased the expression of several genes of tissue remodeling (β-Mhc, Tgfb, Anp, α-Ska) both in vivo and in vitro. These protective effects of Sch B were due to the inhibition of recruitment of MyD88 to TLR2 and TLR4, suppressing the Ang II-induced NF-κB activation and reducing the following inflammatory responses. Moreover, the knockdown of Myd88 in cardiomyocytes abrogated the Ang II-induced increases in the production of inflammatory cytokines and expression of remodeling genes. These findings provide new evidence that the mechanism of Sch B protection was attributed to selective inhibition of MyD88 signaling. This finding could pave the way for novel therapeutic strategies for myocardial inflammatory diseases.
摘要：
心脏组织重塑的特征是心脏组织结构改变和功能障碍。导致心脏衰竭.肾素-血管紧张素-醛固酮系统（RAAS）的持续激活极大地促进了心肌重塑的发展。血管紧张素II（AngII），这是RAAS的主要组成部分，可以通过诱导炎症反应直接导致心脏重塑。五味子B（SchB），从五味子果实中提取的活性成分（Turcz。）Baill已被证明通过其靶向TLR4及其衔接蛋白的能力而表现出抗炎活性，MyD88.在这项研究中,我们探讨了SchB是否通过靶向MyD88减轻AngII诱导的心肌炎症和重塑.SchB显着抑制AngII诱导的炎症，并增加组织重塑的几种基因的表达（β-Mhc，Tgfb,Anp,α-Ska）在体内和体外。SchB的这些保护作用是由于抑制了MyD88向TLR2和TLR4的募集，抑制了AngII诱导的NF-κB激活并减少了随后的炎症反应。此外，Myd88在心肌细胞中的敲减消除了AngII诱导的炎性细胞因子产生和重塑基因表达的增加.这些发现提供了SchB保护机制归因于MyD88信号传导的选择性抑制的新证据。这一发现可能为心肌炎性疾病的新治疗策略铺平道路。
