柚皮素促进Nrf2/Ⅱ相解毒酶活性并降低血管炎症反应  

Naringenin increases Nrf2/phaseⅡdetoxifying enzymes to reduce vascular inflammation

作　　者：董豆豆 张芸 何慧 雷霆雯 欧海龙 DONG Dou-dou;ZHANG Yun;HE Hui;LEI Ting-wen;OU Hai-long(Dept of Biochemistry and Molecular Biology, School of Basic Medical Science, Guizhou Medical University, Guiyang 550025, China)

机构地区：[1]贵州医科大学基础医学院生物化学与分子生物学教研室,贵州贵阳550025

出　　处：《中国药理学通报》2021年第7期1002-1007,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 32060219)。

摘　　要：目的柚皮素对核因子红细胞2相关因子2(Nrf2)/Ⅱ相解毒酶活性的作用及其对血管炎症反应影响的研究。方法Western blot、免疫荧光、逆转录-qPCR检测蛋白的表达。Ⅱ相酶活性检测通过相关试剂盒进行。利用免疫共沉淀技术分析Nrf2与Kelch样环氧氯丙烷相关蛋白1(Keap-1)的相互作用。结果柚皮素促进RAW264.7细胞中Nrf2与Keap-1的解离和核内的聚集,并提高Ⅱ相解毒酶的表达,包括NAD(P)H:醌氧化还原酶1(NQO-1)、谷胱苷肽S-转移酶(GST)和谷胺酸半胱氨酸连接酶(GCL)。同时,柚皮素抑制细胞炎症因子的产生;而Nrf2抑制剂ML385使NQO-1、GST和GCL表达降低、炎症因子的含量提高。另外,检测还发现柚皮素同样通过Nrf2的作用,提高动脉粥样硬化模型小鼠肝脏NQO-1、GST和GCL的表达以及酶的活性,降低主动脉血管的炎症反应。结论柚皮素激活Nrf2,促进相关的Ⅱ相解毒酶活性,从而抑制血管炎症。Aim To investigate the role of naringenin in nuclear factor erythroid 2-related factor 2(Nrf2)/phaseⅡdetoxifying enzyme activities and evaluate its effects on vascular inflammation.Methods Western blot,immunofluorescence and reverse transcription-qPCR were used to detect the protein expression.The activities of phaseⅡdetoxifying enzymes were measured by commercial kits.Immunoprecipitation technology was used to detect the interaction between Nrf2 and kelch-like ECH-associated protein 1(Keap-1).Results Naringenin promoted the dislocation of Nrf2 from Keap-1 and increased Nrf2 nuclear accumulation in RAW264.7 macrophages.Naringenin up-regulated expressions of phaseⅡdetoxifying enzymes such as NAD(P)H quinone oxidoreductase(NQO-1),glutathione S-transferase(GST)and glutamate-cysteine ligase(GCL).It also reduced the levels of cytokines in macrophages.Moreover,the Nrf2 inhibitor ML385 reduced phaseⅡdetoxifying enzyme expressions and increased cytokine levels.In addition,we found naringenin increased the expressions and activities of liver phaseⅡdetoxifying enzymes(NQO-1,GST and GCL)and reduced aortic inflammation in atherosclerotic model mice.The effects were dependent on Nrf2 activity.Conclusions Naringenin activates Nrf2 and promotes phaseⅡdetoxifying enzyme activities,which leads to the inhibition of vascular inflammation.

关 键 词：柚皮素 Ⅱ相解毒酶 NRF2 血管炎症 NAD(P)H醌氧化还原酶 动脉粥样硬化 

分 类 号：R-332[医药卫生] R285.5