Astragalus polysaccharide from Astragalus Melittin ameliorates inflammation via suppressing the activation of TLR-4/NF-κB p65 signal pathway and protects mice from CVB3-induced virus myocarditis
Astragalus polysaccharide from Astragalus Melittin ameliorates inflammation via suppressing the activation of TLR-4/NF-κB p65 signal pathway and protects mice from CVB3-induced virus myocarditis
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DOI：
10.1016/j.ijbiomac.2018.12.207
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发表时间：
2019-04-01
影响因子：
8.2
通讯作者：
Liu, Xiaolei
中科院分区：
文献类型：
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作者：
Liu, Tianlong;Zhang, Mingjie;Liu, Xiaolei
炎症在柯萨奇病毒B3（CVB 3）诱导的心肌炎（VM）中起着重要的调节作用。已有研究表明，黄芪蜂毒肽中的黄芪多糖（AP）可抑制多种病理状态下炎症基因的表达。然而，AP在CVB 3诱导的VM中的功能作用仍然未知。在这里，我们发现AP显著提高了CVB 3诱导小鼠的存活率。AP对CVB 3诱导的小鼠心肌损伤具有保护作用，其主要表现为体重增加，血清肌酸激酶MB（CK-MB）、天冬氨酸转氨酶（AST）和乳酸脱氢酶（LDH）水平降低，左室射血分数（LVEF）和左室短轴缩短率（LVFS）升高。在病理学水平，AP对CVB 3所致的小鼠心肌损伤、扩张型心肌病和慢性心肌纤维化均有改善作用。随后我们发现AP显着抑制CVB 3诱导的心脏炎症标志物（IL-1 β、IL-6、TNF-α、INF-γ和MCP-1）的表达。此外，我们证实AP抑制CVB 3诱导的TLR-4和磷酸化NF-κ B p65在心脏中的表达。以上结果提示，AP对CVB 3诱导的心肌损伤和炎症反应具有保护作用，其机制可能与调节TLR-4/NF-κ B p65信号通路有关，而且AP对CVB 3诱导的TLR-4/NF-κ B p65信号通路的抑制作用不依赖于TNF-α。(C)2018爱思唯尔出版社
Inflammation plays a crucial role in regulating cardiomyopathy and injuries of coxsackievirus B3 (CVB3)-induced viral myocarditis (VM). It has been reported that Astragalus polysaccharide (AP) from Astragalus Melittin could inhabit inflammatory gene expression under a variety of pathological conditions. However, the functional roles of AP in CVB3-induced VM still remain unknown. Here, we found that AP significantly enhanced survival for CVB3-induced mice. AP protected the mice against CVB3-induced myocardial injuries characterized by the increased body weight and depressed serum level of creatine kinase-MB (CK-MB), aspartate transaminases (AST) and lactate dehydrogenase (LDH), enhanced left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS). At the pathological level, AP ameliorated the mice against CVB3-induced myocardial damage, dilated cardiomyopathy and chronic myocardial fibrosis. We subsequently found that AP significantly suppressed CVB3-induced expression of inflammation marker (IL-1 beta, IL-6, TNF-alpha, INF-gamma and MCP-1) in heart. Furthermore, we confirmed that AP suppressed the CVB3-induced expression of TLR-4 and phosphorylated NF-kappa B p65 in heart. Taken together, the data suggest that AP protects against CVB3-induced myocardial damage and inflammation, which may partly attribute to the regulation of TLR-4/NF-kappa B p65 signal pathway, moreover, suppressive effect of AP on CVB3-induced activation of TLR-4/NF-kappa B p65 signal was TNF-alpha-independent. (C) 2018 Published by Elsevier B.V.