王浩, 袁子焰, 石曌玲. 核因子E2相关因子2/血红素加氧酶-1信号在川崎病诱发心肌损伤中的作用[J]. 心脏杂志, 2019, 31(5): 515-520. DOI: 10.12125/j.chj.201905015
    引用本文: 王浩, 袁子焰, 石曌玲. 核因子E2相关因子2/血红素加氧酶-1信号在川崎病诱发心肌损伤中的作用[J]. 心脏杂志, 2019, 31(5): 515-520. DOI: 10.12125/j.chj.201905015
    Hao WANG, Zi-yan YUAN, Zhao-ling SHI. Role of Nrf2/HO-1 in Kawasaki disease-induced myocardial injury[J]. Chinese Heart Journal, 2019, 31(5): 515-520. DOI: 10.12125/j.chj.201905015
    Citation: Hao WANG, Zi-yan YUAN, Zhao-ling SHI. Role of Nrf2/HO-1 in Kawasaki disease-induced myocardial injury[J]. Chinese Heart Journal, 2019, 31(5): 515-520. DOI: 10.12125/j.chj.201905015

    核因子E2相关因子2/血红素加氧酶-1信号在川崎病诱发心肌损伤中的作用

    Role of Nrf2/HO-1 in Kawasaki disease-induced myocardial injury

    • 摘要:
        目的  探讨核因子E2相关因子(Nrf)2/血红素加氧酶(HO)-1信号通路在川崎病(KD)诱发心肌损伤中的作用。
        方法  60只4周龄SD大鼠随机分为对照组、干酪乳杆菌细胞壁成分(LCWE)模拟川崎病组(KD)和叔丁基对苯二酚(TBHQ)干预KD组(KD+TBHQ),每组20只;对照组腹腔注射生理盐水0.5 ml,KD组和KD+TBHQ组腹腔注射LCWE 0.5 ml(1 mg/ml)。4周后,小动物超声检测大鼠心脏功能,酶联免疫吸附法(ELISA)检测心肌组织内丙二醛(MDA)含量、超氧化物歧化酶(SOD)和Caspase-3的活性,Western blot检测心肌组织内Nrf2和HO-1以及凋亡相关蛋白Bcl-2和Bax的蛋白表达水平。
        结果  注射LCWE 4周后,成功制备KD模型鼠。同时发现,与对照组相比,KD组左室射血分数(LVEF)和短轴缩短率(FS)均明显降低(P < 0.05),心肌组织凋亡相关蛋白Bcl-2与Bax比值显著降低(P < 0.05),Caspase-3活性明显升高(P < 0.05),心肌组织中MDA含量增加,而SOD活性降低(P < 0.05),Nrf2和HO-1蛋白表达显著降低(P < 0.05);而应用Nrf2激动剂TBHQ后,可显著改善KD引起的心肌损伤,并且明显降低心肌组织氧化应激程度(P < 0.05)。
        结论  KD抑制心肌中Nrf2/HO-1信号,导致氧化应激程度增强,引起细胞凋亡增加,进而引发心脏损伤,TBHQ激活Nrf2可明显改善KD的上述作用。

       

      Abstract:
        AIM  To investigate the role of Nrf2/HO-1 in Kawasaki disease-induced myocardial injury in the rat model of Kawasaki disease by Lactobacillus casei cell wall extract (LCWE).
        METHODS  Sixty four-week old SD rats were randomly divided into control group, LCWE-induced Kawasaki disease group (LCWE) and TBHQ treatment group (KD+TBHQ). Control group was injected with 0.5 ml saline intraperitoneally, and KD group and KD+TBHQ group were injected with 0.5 ml LCWE (1 mg/ml) intraperitoneally. Four weeks later, rat cardiac functions were tested by ultrasonic testing, and myocardial malondialdehyde (MDA) content and activities of superoxide dismutase (SOD) and caspase-3 were detected by ELISA. Western blot was used to detect the protein level of nuclear factor-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and apoptotic proteins Bcl-2 and Bax.
        RESULTS  Compared with those in control group, the left ventricular ejection fraction (EF) and fractional shortening (FS) were significantly decreased (P < 0.05) and the ratio of Bcl-2 and Bax was also decreased (P < 0.05). The caspase-3 activity and myocardial MDA content were increased (P < 0.05), while SOD activity and protein level of Nrf2 and HO-1 were reduced (P < 0.05). TBHQ, the agonist of Nrf2, alleviated myocardial injury induced by KD and reduced the oxidative stress in myocardium (P < 0.05).
        CONCLUSION  KD can lead to oxidative stress, apoptosis and myocardial injury by inhibiting Nrf2/HO-1. TBHQ activates Nrf2/HO-1 which can inhibit myocardial apoptosis and improve cardiac functions.

       

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