桂皮醛对小鼠柯萨奇病毒诱发病毒性心肌炎的作用

摘要

已知Toll样受体4(Toll-like receptors 4,TLR4)及其下游信号组分在柯萨奇病毒(CoxsackievirusB,CVB)诱发的病毒性心肌炎中扮演重要的角色,其在治疗中的作用仍不明确.桂皮醛具有抗病毒以及成剂量依赖性抑制由TLR4诱导的核因子活性的作用,而其对病毒性心肌炎的作用机制尚不明确.我们的实验结果显示:在体外,桂皮醛对正常心肌细胞的IC50为15 μM;100-1000 μM桂皮醛能显著抑制心肌细胞中的病毒滴度(P<0.01),而细胞存活率与CVB组无统计学差异(P0.01).而在病毒性心肌炎小鼠体内,与模型组比较,20和40mg/kg桂皮醛i.P.使第7 d血清中NO的含量以及心肌中诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS),肿瘤坏死因子(tumor necrosis factor,TNF-α),核因子κB P65(nuclear factor-κB P65,NF-κB P65)和TLR4蛋白质表达显著降低(P<0.05).降低第21 d心脏体重比(HeatWeight/Body Weight,Hw/Bw)比值,提高小鼠生存率,减轻病理损伤的作用.这些结果显示桂皮醛虽在体外无抗病毒活性,但其在体内具有降低病毒滴度和抑制TLR-4-NF-κB信号传导的作用,对病毒性心肌炎小鼠具有治疗作用.桂皮醛可能通过对TLR-4-NF-κB信号传导抑制作用,作为一种新的方法治疗病毒性心肌炎.%It has been demonstrated that Toll-like receptors 4 (TLR4) and their downstream signaling components play a critical role in coxsackievirns-mediated myocarditis, but their therapeutic acation remains indefinite. Cinnamaldehyde is known to possess anti-viral action and inhibite dose dependent NF-κB activation induced by TLR4 or wild-type TLR4.However,little is known regarding the effects of cinnamaldehyde on coxsackievirus B3 (CVB3)-induced viral myocardi-tis. Our studies showed that IC50 value of cinnamaldehyde in normal myocardial cells was only 15 μM in vitro. And cin-namaldehyde can significantly inhibit virus titre (P < 0.01) in myocardial cells by the concentration of 100-1000 μM for 72 hours. And cell survival rate has no difference in statistics between CVB group and cirmamaldehyde group (p 0.01). However,compared with model group,in viral myocarditis mice, cinnamaldehyde(20 and 40 mg/kg i. p. for 7 days) significantly reduced the content of NO in blood serum and such proteins' expression as inducible nitric oxide syn-thase (iNOS) ,tumor necrosis factor(TNF-a), nuclear factor-κB P65 (NF-κB P65)and TLR4(P < 0.05). It also low-ered the ratio of Hw/Bw after 21days and improved survival rate of mice and relieved pathological injury. These results indicated that though cinnamaldehyde had no antiviral activity in vitro, it can lower virus titer and depress TLR-4-NF-κB signal transmission. So we can say that cinnamaldehyde has a therapeutic effect on viral myocarditis mice. Through inhib-iting TLR-4-NF-κB signal transmission cinnamaldelyde may be a new method for treating viral myocarditis.