Department of Pharmacy, Affiliated Hospital of Inner Mongolia Medical University, 010059 Hohhot, PR China.
Department of Pharmacology, College of Pharmacy, Inner Mongolia Medical University, 010059 Hohhot, PR China.
Int J Biol Macromol. 2019 Apr 1;126:179-186. doi: 10.1016/j.ijbiomac.2018.12.207. Epub 2018 Dec 23.
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-1β, IL-6, TNF-α, INF-γ and MCP-1) in heart. Furthermore, we confirmed that AP suppressed the CVB3-induced expression of TLR-4 and phosphorylated NF-κB 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-κB p65 signal pathway, moreover, suppressive effect of AP on CVB3-induced activation of TLR-4/NF-κB p65 signal was TNF-α-independent.
炎症在调节心肌病和柯萨奇病毒 B3 (CVB3) 诱导的病毒性心肌炎 (VM) 损伤中起着至关重要的作用。据报道,黄芪多糖 (AP) 可以抑制多种病理条件下的炎症基因表达。然而,AP 在 CVB3 诱导的 VM 中的功能作用仍不清楚。在这里,我们发现 AP 显著提高了 CVB3 诱导的小鼠的存活率。AP 保护小鼠免受 CVB3 诱导的心肌损伤,表现为体重增加和血清肌酸激酶同工酶-MB (CK-MB)、天冬氨酸转氨酶 (AST) 和乳酸脱氢酶 (LDH) 水平降低,左心室射血分数 (LVEF) 和左心室缩短分数 (LVFS) 升高。在病理水平上,AP 改善了 CVB3 诱导的小鼠心肌损伤、扩张型心肌病和慢性心肌纤维化。随后,我们发现 AP 显著抑制了 CVB3 诱导的心脏中炎症标志物 (IL-1β、IL-6、TNF-α、INF-γ 和 MCP-1) 的表达。此外,我们证实 AP 抑制了 CVB3 诱导的心脏中 TLR-4 和磷酸化 NF-κB p65 的表达。综上所述,数据表明 AP 可预防 CVB3 诱导的心肌损伤和炎症,这可能部分归因于 TLR-4/NF-κB p65 信号通路的调节,此外,AP 对 CVB3 诱导的 TLR-4/NF-κB p65 信号的激活具有抑制作用,且不依赖于 TNF-α。