| 槲皮素对四氯化碳引起的小鼠急性肝损伤治疗作用及其机理 |
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| 作者姓名： | Jia-qi ZHANG ;Liang SHI ;Xi-ning XU ;Si-chong HUANG ;Bin LU ;Li-li JI ;Zheng-tao WANG |
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| 基金项目： | Project supported by the “Shu Guang” Project from Shanghai Municipal Education Commission and Shanghai Education Development Foundation(No.13SG43);the National Natural Science Foundation of China(No.81322053);the Program for New Century Excellent Talents in University(No.NCET-11-1054),China |
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| 摘 要： | 研究目的：本研究旨在观察槲皮素对四氯化碳（CCl4）诱导的肝损伤的治疗解毒作用及其机理。创新要点：首次发现槲皮素对CCl4诱导的肝损伤有治疗作用，并且首次发现Prx和Trx家族参与其中。研究方法：检测小鼠血清转氨酶含量，并检测肝组织中丙二醛（MDA）、谷胱甘肽（GSH）和4．羟基壬烯醛（4-HNE）含量，并用实时聚合酶链式反应（PCR）检测肝组织中Prx1-6、TrxR1／2、Trx1／2、Nrf2和HO．1的mRNA表达情况。重要结论：CCl4造模成功后口服槲皮素对其造成的急性肝损伤有治疗作用，给药组小鼠血清中的转氨酶与模型组相比均有显著下降，通过MDA和免疫组化分析其机理可能和保护氧化应激损伤有关，通过实时PCR分析发现CCl4抑制了抗氧化酶Prx家族、TrxRd1、TrxRd2、Trx1、Trx2和Nrf2及其下游HO-1的基因表达，而槲皮素可以逆转CCl4降低的这些基因的表达。
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| 关 键 词： | 肝毒性 氧应激损伤 Prx Nrf2 TrxRd Trx HO-1 |
| 收稿时间： | 2014 Apr 14 |
Therapeutic detoxification of quercetin against carbon tetrachloride-induced acute liver injury in mice and its mechanism |
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| Jia-qi ZHANG,;Liang SHI,;Xi-ning XU,;Si-chong HUANG,;Bin LU,;Li-li JI,;Zheng-tao WANG.Therapeutic detoxification of quercetin against carbon tetrachloride-induced acute liver injury in mice and its mechanism[J].Journal of Zhejiang University Science,2014,15(12):1039-1047. |
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| Authors: | Jia-qi ZHANG Liang SHI Xi-ning XU Si-chong HUANG Bin LU Li-li JI Zheng-tao WANG |
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| Abstract: | This study observes the therapeutic detoxification of quercetin, a well-known flavonoid, against carbon tetrachlodde （CCI4） induced acute liver injury in vivo and explores its mechanism. QuerceUn decreased CCI4-increased serum activities of alanine and aspartate aminotransferases （ALT/AST） when orally taken 30 min after CCI4 intoxica- tion. The results of a histological evaluation further evidenced the ability of quercetin to protect against CCI4-induced liver injury. Quercetin decreased the CCI4-increased malondialdehyde （MDA） and reduced the glutathione （GSH） amounts in the liver. It also reduced the enhanced immunohistochemical staining of the 4-hydroxynonenal （4-HNE） in the liver induced by CCI4. Peroxiredoxin （Prx） 1, 2, 3, 5, 6, thioredoxin reductase 1 and 2 （TrxRl/2）, thioredoxin 1 and 2 （Trxl/2）, nuclear factor erythroid 2-related factor 2 （Nrf2）, and heme oxygenase-1 （HO-1） all play critical roles in maintaining cellular redox homeostasis. Real-time polymerase chain reaction （PCR） results demonstrated that quercetin reversed the decreased mRNA expression of all those genes induced by CCI4. In conclusion, our results demonstrate that quercetin ameliorates CCI4-induced acute liver injury in vivo via alleviating oxidative stress injuries when orally taken after CCI4 intoxication. This protection may be caused by the elevation of the antioxidant capacity induced by quercetin. |
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| Keywords: | Hepatotoxicity Oxidative stress Peroxiredoxin （Prx） Nuclear factor erythroid 2-related factor 2 （Nrf2） TrxR Trx HO-1 |
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