天然产物研究与开发
天然產物研究與開髮
천연산물연구여개발
NATURAL PRODUCT RESEARCH AND DEVELOPMENT
2010年
5期
769-776
,共8页
丁媛媛%赵钢涛%杨凡%王四旺
丁媛媛%趙鋼濤%楊凡%王四旺
정원원%조강도%양범%왕사왕
桂皮醛%抗病毒%柯萨奇病毒B3%病毒性心肌炎%Toll样受体4
桂皮醛%抗病毒%柯薩奇病毒B3%病毒性心肌炎%Toll樣受體4
계피철%항병독%가살기병독B3%병독성심기염%Toll양수체4
Cinnamaldehyde%Anti-viral%CVB3%Viral Myocarditis%TLR4
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.
已知Toll樣受體4(Toll-like receptors 4,TLR4)及其下遊信號組分在柯薩奇病毒(CoxsackievirusB,CVB)誘髮的病毒性心肌炎中扮縯重要的角色,其在治療中的作用仍不明確.桂皮醛具有抗病毒以及成劑量依賴性抑製由TLR4誘導的覈因子活性的作用,而其對病毒性心肌炎的作用機製尚不明確.我們的實驗結果顯示:在體外,桂皮醛對正常心肌細胞的IC50為15 μM;100-1000 μM桂皮醛能顯著抑製心肌細胞中的病毒滴度(P<0.01),而細胞存活率與CVB組無統計學差異(P0.01).而在病毒性心肌炎小鼠體內,與模型組比較,20和40mg/kg桂皮醛i.P.使第7 d血清中NO的含量以及心肌中誘導型一氧化氮閤酶(inducible nitric oxide synthase,iNOS),腫瘤壞死因子(tumor necrosis factor,TNF-α),覈因子κB P65(nuclear factor-κB P65,NF-κB P65)和TLR4蛋白質錶達顯著降低(P<0.05).降低第21 d心髒體重比(HeatWeight/Body Weight,Hw/Bw)比值,提高小鼠生存率,減輕病理損傷的作用.這些結果顯示桂皮醛雖在體外無抗病毒活性,但其在體內具有降低病毒滴度和抑製TLR-4-NF-κB信號傳導的作用,對病毒性心肌炎小鼠具有治療作用.桂皮醛可能通過對TLR-4-NF-κB信號傳導抑製作用,作為一種新的方法治療病毒性心肌炎.
이지Toll양수체4(Toll-like receptors 4,TLR4)급기하유신호조분재가살기병독(CoxsackievirusB,CVB)유발적병독성심기염중분연중요적각색,기재치료중적작용잉불명학.계피철구유항병독이급성제량의뢰성억제유TLR4유도적핵인자활성적작용,이기대병독성심기염적작용궤제상불명학.아문적실험결과현시:재체외,계피철대정상심기세포적IC50위15 μM;100-1000 μM계피철능현저억제심기세포중적병독적도(P<0.01),이세포존활솔여CVB조무통계학차이(P0.01).이재병독성심기염소서체내,여모형조비교,20화40mg/kg계피철i.P.사제7 d혈청중NO적함량이급심기중유도형일양화담합매(inducible nitric oxide synthase,iNOS),종류배사인자(tumor necrosis factor,TNF-α),핵인자κB P65(nuclear factor-κB P65,NF-κB P65)화TLR4단백질표체현저강저(P<0.05).강저제21 d심장체중비(HeatWeight/Body Weight,Hw/Bw)비치,제고소서생존솔,감경병리손상적작용.저사결과현시계피철수재체외무항병독활성,단기재체내구유강저병독적도화억제TLR-4-NF-κB신호전도적작용,대병독성심기염소서구유치료작용.계피철가능통과대TLR-4-NF-κB신호전도억제작용,작위일충신적방법치료병독성심기염.
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.
