牛舌草总黄酮通过ROS/TXNIP/NLRP3抑制炎症小体活化抗心肌缺血再灌注损伤

阴苏月, 姜瑜, 王丹姝, 燕柳艳, 王守宝, 杜冠华

中国药学杂志 ›› 2021, Vol. 56 ›› Issue (14) : 1131-1137.

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中国药学杂志 ›› 2021, Vol. 56 ›› Issue (14) : 1131-1137. DOI: 10.11669/cpj.2021.14.004
论著

牛舌草总黄酮通过ROS/TXNIP/NLRP3抑制炎症小体活化抗心肌缺血再灌注损伤

  • 阴苏月, 姜瑜, 王丹姝, 燕柳艳, 王守宝*, 杜冠华*
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Total Flavonoids of Anchusa italica Retz. Inhibit Activation of Inflammasome through ROS/TXNIP/NLRP3 Pathway to Protect against Myocardial Ischemia-reperfusion Injury

  • YIN Su-yue, JIANG Yu, WANG Dan-shu, YAN Liu-yan, WANG Shou-bao*, DU Guan-hua*
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摘要

目的 从炎症小体活化和活性氧/硫氧还蛋白互作蛋白/NOD样受体蛋白3(ROS/TXNIP/NLRP3)通路考察牛舌草总黄酮(total flavonoids of Anchusa italica Retz., TF)抗心肌缺血再灌注损伤的作用机制。方法 小鼠采用冠状动脉左前降支结扎模型模拟心肌缺血再灌注(ischemia/reperfusion, I/R)损伤。将模型制备成功的30只小鼠随机分为模型组(I/R)、TF 30 mg·kg-1处理组(I/R+TF30)和100 mg·kg-1处理组(I/R+TF100),再灌同时给予生理盐水、TF。于再灌注24 h时,检测小鼠心功能,测定心肌梗死范围和血清心肌酶谱,心肌冰冻切片染色观察活性氧(ROS)水平,Western blotting分析NLRP3炎症小体活化以及TXNIP与NLRP3相互作用的变化。结果 TF在剂量为30和100 mg·kg-1时均可改善心功能,减少心肌梗死范围,降低血清心肌酶水平。另外,TF处理减少心肌炎症因子白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)α含量,降低心肌ROS水平。TF在30和100 mg·kg-1均显著降低TXNIP、NLRP3、cleaved caspase-1和cleaved IL-1β,并抑制TXNIP/NLRP3相互作用。结论 牛舌草总黄酮通过抑制ROS/TXNIP/NLRP3通路,从而减轻NLRP3炎症小体活化,发挥抗心肌缺血再灌注损伤作用。

Abstract

OBJECTIVE To investigate the role of activation of NLRP3 inflammasome and ROS/TXNIP/NLRP3 pathway in the effects of total flavonoids of Anchusa italica Retz. (TF) against myocardial ischemia-reperfusion injury (MIRI). METHODS The ligation of left coronary artery was used to mimic MIRI in mice. Thirty mice were randomly divided into I/R group, 30 mg·kg-1 TF treatment group (I/R+TF30) and 100 mg·kg-1 treatment group (I/R+TF100). At 24 h after reperfusion, cardiac function, myocardial infarct index and serum myocardial enzyme were measured. The activation of NLRP3 inflammasome, ROS level and TXNIP/NLRP3 interaction were observed. RESULTS TF treatment at the doses of 30 and 100 mg·kg-1 improved cardiac function, reduced myocardial infarct index, showing obvious myocardial protection. In addition, TF treatment reduced the levels of inflammatory cytokines IL-1 β, IL-6 and TNF-α, and decreased ROS content in myocardial tissue. The levels of TXNIP, NLRP3, cleaved caspase-1 and cleaved IL-1 β were significantly decreased in I/R+TF30 and I/R+TF100 groups, and the TXNIP/NLRP3 interaction was also inhibited as compared with I/R group. CONCLUSION TF treatment exertes potent protection against MIRI in mice, in which inhibition of activation of NLRP3 inflammasome via the ROS/TXNI/NLRP3 pathway played a pivotal role.

关键词

牛舌草总黄酮 / 心肌缺血再灌注损伤 / NOD样受体蛋白3炎症小体 / 活性氧 / 硫氧还蛋白互作蛋白/NOD样受体蛋白3相互作用

Key words

total flavonoids of Anchusa italica Retz. (TF) / myocardial ischemia-reperfusion injury (MIRI) / NLRP3 inflammasome / reactive oxygen species (ROS) / TXNIP/NLRP3 pathway

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阴苏月, 姜瑜, 王丹姝, 燕柳艳, 王守宝, 杜冠华. 牛舌草总黄酮通过ROS/TXNIP/NLRP3抑制炎症小体活化抗心肌缺血再灌注损伤[J]. 中国药学杂志, 2021, 56(14): 1131-1137 https://doi.org/10.11669/cpj.2021.14.004
YIN Su-yue, JIANG Yu, WANG Dan-shu, YAN Liu-yan, WANG Shou-bao, DU Guan-hua. Total Flavonoids of Anchusa italica Retz. Inhibit Activation of Inflammasome through ROS/TXNIP/NLRP3 Pathway to Protect against Myocardial Ischemia-reperfusion Injury[J]. Chinese Pharmaceutical Journal, 2021, 56(14): 1131-1137 https://doi.org/10.11669/cpj.2021.14.004
中图分类号: R965   

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基金

“重大新药创制”科技重大专项资助(2018ZX09711001-010);国家自然科学基金面上项目资助(81673422); 北京市自然科学基金面上项目资助(7192131)
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