查耳酮衍生物L2H24对H2O2诱导损伤的心肌细胞的保护作用

doi:10.3969/j.issn.2095-9400.2021.07.003

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摘要目的：探讨查耳酮衍生物L2H24 对H2O2 诱导氧化损伤的心肌细胞的抗氧化保护作用及其相关分子机制。方法：MTT法检测大鼠心肌细胞H9c2 活性；集落克隆实验检测细胞增殖能力；倒置显微镜下观察细胞焦亡形态学变化；硫代巴比妥酸显色反应检测细胞中脂质过氧化MDA水平；Western blot法检测HO-1、核/浆Nrf2、Caspase-1 p48、Caspase-1 p20、IL-1β的表达水平。结果：L2H24能上调H2O2氧化损伤的H9c2细胞的存活率（P ＜0.05），促进其细胞集落形成，降低其MDA水平（P ＜0.05），减少细胞中Caspase-1 p48、Caspase-1 p20、IL-1β的表达水平（P ＜0.05），改善细胞焦亡现象；能促进细胞中Nrf2易位入核，并上调其下游抗氧化蛋白HO-1的表达水平（P ＜0.05），对H2O2诱导氧化损伤的心肌细胞起到保护作用。结论：查耳酮衍生物L2H24具有抗氧化损伤作用，其机制可能与激活Nrf2/HO-1信号通路有关。

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	胡琳雅
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	何文斐
	吴建章

关键词 ：查耳酮衍生物, 心肌细胞, 氧化应激, 抗氧化保护作用

Abstract：Objective: To investigate the anti-oxidative protective effect of chalcone derivative L2H24 on H2O2-induced H9c2 cardiomyocytes injury and its related molecular mechanism. Methods: The survival rate of cardiomyocytes was detected by MTT experiment; cell proliferation ability was detected by colony cloning experiment; cell pyroptosis was observed under the inverted microscope; MDA level of lipid peroxidation in cells was detected by thiobarbituric acid color reaction; the expression level of HO-1, Nrf2, Caspase-1 p48, Caspase-1 p20 and IL-1β in the cells was measured by Western blotting analysis. Results: L2H24 not only increased the survival rate of H9c2 cells damaged by H2O2 (P<0.05), promote the formation of cell colonies and reduce the level of cell lipid peroxidation (P<0.05), but also reduced the expression level of Caspase-1 p48, Caspase-1 p20 and IL-1β in cells (P<0.05) and improved the pyrolysis. Furthermore, L2H24 promoted the translocation of Nrf2 into the nucleus and up-regulated the expression level of its downstream antioxidant protein HO-1, which protected cardiomyocytes from H2O2-induced oxidative damage. Conclusion: Chalcone derivative L2H24 plays a protective role against oxidative damage, and its mechanism may be related to the activation of Nrf2/HO-1 signaling pathway.

Key words： chalcone derivatives cardiomyocytes oxidative stress antioxidant protection

收稿日期: 2021-01-20

基金资助:浙江省自然科学基金资助项目（ L G F 2 0 H 3 1 0 0 0 2 ，LQ18H280008）。

通讯作者: 何文斐，副教授 E-mail: wenfeihe@126.com。

作者简介: 胡琳雅，硕士生，Email：1208607862@qq.com。

链接本文:

https://xb.wmu.edu.cn/CN/10.3969/j.issn.2095-9400.2021.07.003 或 https://xb.wmu.edu.cn/CN/Y2021/V51/I7/534

[1] HO E, KARIMI GALOUGAHI K, LIU C C, et al. Biological markers of oxidative stress: Applications to cardiovascular research and practice[J]. Redox Biol, 2013, 1(1): 483-491.
[2] WANG W, KANG P M. Oxidative stress and antioxidant treatments in cardiovascular diseases[J]. Antioxidants(Basel), 2020, 9(12): 1292.
[3] SACK M N, FYHRQUIST F Y, SAIJONMAA O J, et al.Basic biology of oxidative stress and the cardiovascular system: Part 1 of a 3-part series[J]. J Am Coll Cardiol, 2017,70(2): 196-211.
[4] SILVA-PALACIOS A, KöNIGSBERG M, ZAZUETA C.Nrf2 signaling and redox homeostasis in the aging heart:A potential target to prevent cardiovascular diseases?[J].Ageing Res Rev, 2016, 26: 81-95.
[5] PADHYE S, AHMAD A, OSWAL N, et al. Emerging role of Garcinol, the antioxidant chalcone from Garcinia indica Choisy and its synthetic analogs[J]. J Hematol Oncol, 2009,2: 38.
[6] MAHAPATRA D K, BHARTI S K, ASATI V. Chalcone derivatives: anti-inflammatory potential and molecular targets perspectives[J]. Curr Top Med Chem, 2017, 17(28):3146-3169.
[7] VENTURELLI S, BURKARD M, BIENDL M, et al.Prenylated chalcones and flavonoids for the prevention and treatment of cancer[J]. Nutrition, 2016, 32(11-12): 1171-1178.
[8] NOWAKOWSKA Z. A review of anti-infective and antiinflammatory chalcones[J]. Eur J Med Chem, 2007, 42(2):125-137.
[9] WANG J, HUANG L, CHENG C, et al. Design, synthesis and biological evaluation of chalcone analogues with novel dual antioxidant mechanisms as potential anti-ischemic stroke agents[J]. Acta Pharm Sin B, 2019, 9(2): 335-350.
[10] LIN Y, ZHANG M, LU Q, et al. A novel chalcone derivative exerts anti-inflammatory and anti-oxidant effects after acute lung injury[J]. Aging (Albany NY), 2019, 11(18): 7805-7816.
[11] CHEN J, ZENG L, XIA T, et al. Toward a biomarker of oxidative stress: a fluorescent probe for exogenous and endogenous malondialdehyde in living cells[J]. Anal Chem,2015, 87(16): 8052-8056.
[12] 杨美娟, 虞天一, 乔东艳, 等. H2O2 诱导人滋养细胞HTR-8/SVneo焦亡模型的建立[J]. 医学研究生学报, 2020, 33(8):820-825.
[13] ZHUANG C, ZHANG W, SHENG C, et al. Chalcone: A privileged structure in medicinal chemistry[J]. Chem Rev,2017, 117(12): 7762-7810.
[14] R A N I A , A N A N D A , K U M A R K , e t a l . R e c e n t developments in biological aspects of chalcones: the odyssey continues[J]. Expert Opin Drug Discov, 2019, 14(3): 249-288.
[15] MAHAPATRA D K, BHARTI S K. Therapeutic potential of chalcones as cardiovascular agents[J]. Life Sci, 2016, 148:154-172.
[16] ZHANG X, ZHU P, ZHANG X, et al. Natural antioxidantisoliquiritigenin ameliorates contractile dysfunction of hypoxic cardiomyocytes via AMPK signaling pathway[J].Mediators Inflamm, 2013, 2013: 390890.
[17] GU X, SHI Y, CHEN X, et al. Isoliquiritigenin attenuates diabetic cardiomyopathy via inhibition of hyperglycemiainduced inflammatory response and oxidative stress[J].Phytomedicine, 2020, 78: 153319.
[18] 覃斐章, 黄媛恒, 陈兆霓, 等. JAK2/STAT3 信号通路介导玉郎伞查尔酮后处理对大鼠离体心脏的保护作用[J]. 中国实验方剂学杂志, 2017, 23(24): 153-158.
[19] YOU S, QIAN J, SUN C, et al. An Aza resveratrol-chalcone derivative 6b protects mice against diabetic cardiomyopathy by alleviating inflammation and oxidative stress[J]. J Cell Mol Med, 2018, 22(3): 1931-1943.
[20] NAGABABU E, MOHANTY J G, FRIEDMAN J S, et al.Role of peroxiredoxin-2 in protecting RBCs from hydrogen peroxide-induced oxidative stress[J]. Free Radic Res, 2013,47(3): 164-171.
[21] SHI J, GAO W, SHAO F. Pyroptosis: gasdermin-mediated programmed necrotic cell death[J]. Trends Biochem Sci,2017, 42(4): 245-254.
[22] 白植标. 活性氧对人退变椎间盘髓核细胞焦亡的影响及其调控机制研究[D]. 重庆: 重庆医科大学, 2020.
[23] CERRETTI D, KOZLOSKY C, MOSLEY B, et al. Molecular cloning of the interleukin-1 beta converting enzyme[J].Science, 1992, 256(5053): 97-100.
[24] THORNBERRY N, BULL H, CALAYCAY J, et al. A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes[J]. Nature, 1992, 356(6372):768-74.
[25] SHEN Y, LIU X, SHI J, et al. Involvement of Nrf2 in myocardial ischemia and reperfusion injury[J]. Int J Biol Macromol, 2019, 125: 496-502.
[26] CHENG L, JIN Z, ZHAO R, et al. Resveratrol attenuates inflammation and oxidative stress induced by myocardial ischemia-reperfusion injury: role of Nrf2/ARE pathway[J].Int J Clin Exp Med, 2015, 8(7): 10420-10428.
[27] OYAKE T, ITOH K, MOTOHASHI H, et al. Bach proteins belong to a novel family of BTB-basic leucine zipper transcription factors that interact with MafK and regulate transcription through the NF-E2 site[J]. Mol Cell Biol, 1996,16(11): 6083-6095.
[28] VILLENEUVE N F, LAU A, ZHANG D D. Regulation of the Nrf2-Keap1 antioxidant response by the ubiquitin proteasome system: an insight into cullin-ring ubiquitin ligases[J]. Antioxid Redox Signal, 2010, 13(11): 1699-1712.
[29] BUENDIA I, MICHALSKA P, NAVARRO E, et al. Nrf2-ARE pathway: An emerging target against oxidative stress and neuroinflammation in neurodegenerative diseases[J].Pharmacol Ther, 2016, 157: 84-104.
[30] SRISOOK K, KIM C, CHA Y N. Molecular mechanisms involved in enhancing HO-1 expression: de-repression by heme and activation by Nrf2, the “one-two” punch[J].Antioxid Redox Signal, 2005, 7(11-12): 1674-1687.
[31] ZHOU B, ZHANG J Y, LIU X S, et al. Tom20 senses ironactivated ROS signaling to promote melanoma cell pyroptosis [J]. Cell Res, 2018, 28(12): 1171-1185.
[32] WANG Y, SHI P, CHEN Q, et al. Mitochondrial ROS promote macrophage pyroptosis by inducing GSDMD oxidation[J]. J Mol Cell Biol, 2019, 11(12): 1069-1082.