萝卜硫素对阿霉素急性肝损伤小鼠的保护作用及对PPARa、NF-κb的影响

详细信息    查看全文 | 推荐本文 |

英文篇名：Protective effect of sulforaphane on mice with acute liver injury induced by adriamycin and its effect on PPARa and NF-κb 作者：纪倩 ; 王琦 ; 茹仁萍 ; 李松龙 ; 包剑锋 英文作者：JI Qian;WANG Qi;RU Ren-ping;LI Song-long;BAO Jian-feng;Xixi Hospital Affiliated to Zhejiang Chinese Medical University; 关键词：萝卜硫素 ; 阿霉素 ; 急性肝损伤 ; 过氧化物酶体增殖物激活受体 ; 核转录因子-κb 英文关键词：Sulforaphane;;Adriamycin;;Acute liver injury;;PPARa;;NF-κb 中文刊名：ZWJZ 英文刊名：Chinese Journal of Health Laboratory Technology 机构：浙江中医药大学附属杭州市西溪医院; 出版日期：2019-01-25 出版单位：中国卫生检验杂志 年：2019 期：v.29 语种：中文; 页：ZWJZ201902005 页数：4 CN：02 ISSN：41-1192/R 分类号：25-28

摘要

目的研究萝卜硫素(SFN)对ICR小鼠阿霉素(ADM)急性肝损伤的保护作用及对PPARa、NF-κb的影响。方法小鼠腹腔注射20 mg/kg阿霉素致小鼠急性肝损伤,以小鼠体质量、脏器指数变化情况、血清生化指标和病理变化评价萝卜硫素的保护作用,并以RT-PCR法检测肝组织中PPARa mRNA、NF-κb mRNA的表达变化。结果萝卜硫素组能明显缓解阿霉素引起的体质量减轻,降低阿霉素诱导的肝、心、肾指数升高。与模型组比较,各预保护组能明显缓解阿霉素致小鼠血清ALT、AST水平的升高,差异有统计学意义(P <0. 05);病理切片显示各预保护组肝组织损伤明显减轻; RT-PCR显示与模型组比较,预保护组和SFN组PPARa mRNA显著升高(P <0. 05),Nf-κb mRNA显著降低,差异均有统计学意义(P <0. 05)。结论萝卜硫素对阿霉素所致的小鼠急性肝损伤具有保护作用,与激活PPARa,降低Nf-κb,参与脂质代谢和炎症反映有关。
        Objective To study the protective effect of sulforaphane( SFN) on acute liver injury of adriamycin( ADM) in ICR mice and the effect on PPARa NF-κb. Methods Acute liver injury was induced by intraperitoneal injection of 20 mg/kg adriamycin in mice. The protective effect of sulforaphane was evaluated by the changes of body weight,organ index,serum biochemical indexes and pathological changes. The expression changes of NF-κb mRNA and PPARa mRNAs in liver tissue were detected by RT-PCR method. Results Sulforaphane could significantly alleviate the weight loss induced by adriamycin and decrease the liver,heart and kidney fingers index induced by doxorubicin. Compared with the model group,each pre-protection group could significantly alleviate the elevation of serum ALT and AST levels induced by adriamycin,with the differences statistically significant( P < 0. 05); and the pathological sections showed that the liver tissue injury in each pre-protection group was significantly alleviated compared with the model group. RT-PCR revealed that PPARa mRNA in pre-protection group and SFN group significantly increased( P < 0. 05); while Nf-κb mRNA decreased significantly,with the differences statistically significant( P < 0. 05). Conclusion Sulforaphane has protective effect on acute liver injury induced by doxorubicin in mice,which is associated with the activation of PPARa,decrease of Nf-κb,involvement in lipid metabolism and inflammatory response.

引文

[1] Benjamin RS,Wiernik PH,Bachur NR. Efficacy,safety,and pharmacologic basis of an intermittent single high dose schedule[J]. Cancer,1974,33(1):19-27.
    [2] Abbaoui B,Riedl KM,Ralston RA,et al. Inhibition of bladder cancer by broccoli isothiocyanates sulforaphane and erucin:Characterization,metabolism,and interconversion[J]. Mol Nutr Food Res,2012,56(11):1675-1687.
    [3]贾侃,贺云冲,洪姣,等.西兰花提取物萝卜硫素抑制肺癌细胞的生长和侵袭[J].中国保健营养,2014(7):4589-4550.
    [4] Oh CJ,Kim JY,Park AK,et al. Sulforaphane attenuates hepatic fibrosis via NF-E2-related factor 2-mediated inhibition of transforming growth factor-β/Smad signaling[J]. Free Radic Biol Med,2012,52(3):671-682.
    [5] Abou-Alfa GK,Johnson P,Knox JJ,et al. Doxorubicin plus sorafenib vs doxorubicin alone in patients with advanced hepatocellular carcinoma:a randomized trial[J]. JAMA,2010,304(19):2154-2160.
    [6] Fimognari C,Lenzi M,Sciuscio D,et al. Combination of Doxorubicin and Sulforaphane for Reversing Doxorubicin-Resistant Phenotype in Mouse Fibroblasts with p53 Ser220 Mutation[J]. Ann N Y Acad Sci,2007,1095:62-69.
    [7]曲震理.萝卜硫素对阿霉素所致体外培养心肌细胞凋亡的影响[J].社区医学杂志,2014,12(2):47-48.
    [8] Teodoro BG,Natali AJ,Fernandes SA,et al. Improvements of atherosclerosis and hepatic Oxidative stress are independent of exercise intensity in LDLr(-/-)mice[J]. J Atheroscler Thromb,2012,19(10):904-911.
    [9]罗敏.过氧化物酶体增殖物激活受体α在肝脏代谢性疾病和肝毒性中的研究进展[J].中西医结合肝病杂志,2016,26(2):124-127.
    [10] Patterson AD,Shah YM,Matsubara T,et al. Peroxisome proliferator-activated receptor alpha induction of uncoupling protein 2 protects against acetaminophen-induced liver toxicity[J]. Hepatology,2012,56(1):281-290.
    [11] Chen K,Li YH,Xu SQ,et al. Protective effects of peroxi-some proliferators-activated receptor'o/agonist,Wy 14643,on hypoxia/reoxygenation injury in primary rat hepatocytes[J]. PPAR Res,2012,2012:547980.
    [12]秦金东,高芳,李学峰,等.吡咯烷二硫代氨基甲酸酯对免疫性肝损伤小鼠NF-κB的影响[J].中国卫生检验杂志,2016,26(4):494-496.