Wang Tuanjie, Zhang Jian, Xiao Aiju, Liu Weiqing, Shang Yun, An Jindou
PICU, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, Henan Province, China.
PICU, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, Henan Province, China.
Biochem Biophys Res Commun. 2016 Nov 4;480(1):126-131. doi: 10.1016/j.bbrc.2016.09.135. Epub 2016 Sep 28.
Viral myocarditis (VMC) is characterized as an inflammatory process of the myocardium and can be fatal in infants and children. Melittin is a major polypeptide in honey bee venom that has been traditionally used against inflammation. However, its effect on VMC and the underlying molecular mechanism has not been reported. In this study, BALB/c mice were intraperitoneally injected with CVB3 to build a VMC model and treated with melittin. The results showed that melittin increased the mice's body weight and inhibited CVB3 replication. HE staining also showed that melittin alleviated myocardial injury in the VMC model. Flow cytometry showed that melittin inhibited myocardial cell apoptosis; in addition, real-time PCR showed that melittin decreased the expression of bax and caspase-3, and increased the expression of bcl-2. The results of echocardiographic examination showed that melittin improved cardiac function. Moreover, melittin decreased the activity of AST, CK, HBDH and LDH, and decreased the production of IL-1β, IL-6, TNF-α and MCP-1 in CVB3-induced myocardial tissues. Finally, we also found that melittin increased the expression of HDAC2 and activated the GSK-3β/Nrf2/ARE signaling pathway, whereas these changes were reversed by inhibition of HDAC2 in VMC model mice. In conclusion, our results suggested that melittin ameliorates CVB3-induced myocarditis via activation of the HDAC2-mediated GSK-3β/Nrf2/ARE signaling pathway.
病毒性心肌炎（VMC）的特征是心肌的炎症过程，在婴幼儿中可能是致命的。蜂毒明肽是蜜蜂毒液中的一种主要多肽，传统上用于抗炎。然而，其对VMC的作用及潜在分子机制尚未见报道。在本研究中，给BALB/c小鼠腹腔注射柯萨奇病毒B3（CVB3）以建立VMC模型，并给予蜂毒明肽治疗。结果显示，蜂毒明肽增加了小鼠体重并抑制了CVB3复制。苏木精-伊红（HE）染色还显示，蜂毒明肽减轻了VMC模型中的心肌损伤。流式细胞术显示，蜂毒明肽抑制心肌细胞凋亡；此外，实时荧光定量聚合酶链反应（real-time PCR）显示，蜂毒明肽降低了bax和半胱天冬酶-3（caspase-3）的表达，并增加了bcl-2的表达。超声心动图检查结果显示，蜂毒明肽改善了心脏功能。此外，蜂毒明肽降低了天冬氨酸转氨酶（AST）、肌酸激酶（CK）、α-羟丁酸脱氢酶（HBDH）和乳酸脱氢酶（LDH）的活性，并减少了CVB3诱导的心肌组织中白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和单核细胞趋化蛋白-1（MCP-1）的产生。最后，我们还发现，蜂毒明肽增加了组蛋白去乙酰化酶2（HDAC2）的表达并激活了糖原合成酶激酶-3β（GSK-3β）/核因子E2相关因子2（Nrf2）/抗氧化反应元件（ARE）信号通路，而在VMC模型小鼠中抑制HDAC2可逆转这些变化。总之，我们的结果表明，蜂毒明肽通过激活HDAC2介导的GSK-3β/Nrf2/ARE信号通路改善CVB3诱导的心肌炎。
