留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

胆绿素治疗作用的研究进展

白文娅 杨渊 霍思颖 杨鑫 邵建林

白文娅, 杨渊, 霍思颖, 杨鑫, 邵建林. 胆绿素治疗作用的研究进展[J]. 昆明医科大学学报, 2022, 43(6): 147-153. doi: 10.12259/j.issn.2095-610X.S20220601
引用本文: 白文娅, 杨渊, 霍思颖, 杨鑫, 邵建林. 胆绿素治疗作用的研究进展[J]. 昆明医科大学学报, 2022, 43(6): 147-153. doi: 10.12259/j.issn.2095-610X.S20220601
Wenya BAI, Yuan YANG, Siying HUO, Xin YANG, Jianlin SHAO. Advances in Research Progress on the Therapeutic Function of Biliverdin[J]. Journal of Kunming Medical University, 2022, 43(6): 147-153. doi: 10.12259/j.issn.2095-610X.S20220601
Citation: Wenya BAI, Yuan YANG, Siying HUO, Xin YANG, Jianlin SHAO. Advances in Research Progress on the Therapeutic Function of Biliverdin[J]. Journal of Kunming Medical University, 2022, 43(6): 147-153. doi: 10.12259/j.issn.2095-610X.S20220601

胆绿素治疗作用的研究进展

doi: 10.12259/j.issn.2095-610X.S20220601
基金项目: 国家自然科学基金资助项目(81960250);云南省教育厅科研基金资助项目(2022J0192);云岭产业技术领军人才项目(YLXL20170054)
详细信息
    作者简介:

    白文娅(1993~),女,山东菏泽人,在读博士研究生,住院医师,主要从事围术期器官保护工作

    通讯作者:

    杨鑫,E-mail: 1817415847@qq.com

    邵建林,E-mail: cmushaoji@aliyun.com

  • 中图分类号: R614.2

Advances in Research Progress on the Therapeutic Function of Biliverdin

  • 摘要: 胆绿素、胆红素是血红素代谢的产物。有研究发现,胆绿素依靠胆绿素-胆红素氧化还原系统,不断地消耗氧自由基,激活胆绿素还原酶,从而发挥抗氧化、抗炎、抑制免疫反应、稳定血管内皮细胞、调控细胞凋亡等作用。将从胆绿素、胆红素的结构与代谢、胆绿素的作用及机制等方面作一综述。
  • 图  1  胆绿素、胆红素氧化还原系统

    注:血红素在HO-1、CPR的作用下,生成胆绿素、一氧化碳(CO)、铁离子(Fe2+),接着胆绿素又在BVR的作用下还原成胆红素,胆红素又可通过和ROS反应,氧化成胆绿素。HO-1:血红素氧合酶1;CPR:细胞色素P450还原酶;BVR:胆绿素还原酶;ROS:活性氧自由基;NADPH:烟酰胺腺嘌呤二核苷酸磷酸;CO:一氧化碳。

    Figure  1.  The biliverdin-bilirubin redox recycling system

    图  2  胆绿素作用及机制图

    注:PI3K/Akt信号通路:磷脂酰肌醇-3-激酶/蛋白激酶B;MAPK信号通路: p38促分裂原活化的蛋白激酶;NF-κB信号通路:核因子κB信号通路;NLRP3:核苷酸寡聚结合域样受体热蛋白结构域相关蛋白 3;NFAT:活化T细胞核因子;AAG:α1-酸糖蛋白。

    Figure  2.  Role of biliverdin in different pathophysiological processes

  • [1] Agnieszka Loboda, Agnieszka Jazwa, Anna Grochot-Przeczek, et al. Heme oxygenase-1 and the vascular bed: From molecular mechanisms to therapeutic opportunities[J]. Antioxid Redox Signal, 2008, 10(10): 1767-1812.
    [2] Andrew C Bulmer,Joanne T Blanchfifield,Istvan Toth. In vitro permeability and metabolic stability of bile pigments and the effffects of hydrophilic and lipophilic modifification of biliverdin[J]. Bioorg Me Chem,2008,16(7):3616-3625. doi: 10.1016/j.bmc.2008.02.008
    [3] Daniel Hanley. Eggshell-derived Biliverdin as an Antioxidant Defense System for Birds’ Eggs[J]. Bioessays,2020,42(8):e2000133. doi: 10.1002/bies.202000133
    [4] Tao Zhang,Hehe Liu,Jiwen Wang,et al. Evidences in duck (Anas platyrhynchos) by transcriptome data for supporting the biliverdin was mainly synthesized by shell gland[J]. Poult Sci,2019,98(5):2260-2271. doi: 10.3382/ps/pey576
    [5] Ryan G. Shiels, Wenu Hewage, Josif Vidimce, et al. Bulmer. Pharmacokinetics of bilirubin -10- sulfonate and biliverdin in the rat[J]. Eur J Pharm Sci, 2021, 159期号: 105684.

    Ryan G Shiels,Wenu Hewage,Josif Vidimce,et al. Bulmer. Pharmacokinetics of bilirubin -10- sulfonate and biliverdin in the rat[J]. Eur J Pharm Sci,2021,159:105684.
    [6] Masakazu Sugishim, Kei Wada, Masaki Unno, et al. Bilin metabolizing enzymes: site-specifific reductions catalyzed by two different type of enzymes[J]. Curr Opin Struct Biol, 2019, 59期号: 73-80.

    Masakazu Sugishim,Kei Wada,Masaki Unno,et al. Bilin metabolizing enzymes:site-specifific reductions catalyzed by two different type of enzymes[J]. Curr Opin Struct Biol,2019,59:73-80.
    [7] Beibei Zhang,Natasha M. Nesbitt,Pedro José Barbosa Pereira,et al. Biochemical characterization of biliverdins IXβ/δ generated by a selective heme oxygenase[J]. Biochem J,2020,477(3):601-614. doi: 10.1042/BCJ20190810
    [8] Ryan G Shiels,Josif Vidimce,Ben Matthews,et al. Unprecedented microbial conversion of biliverdin into bilirubin-10-sulfonate[J]. Sci Rep,2019,9(1):2988. doi: 10.1038/s41598-019-39548-w
    [9] 柳军,张陆勇. 胆红素及其类似物的结构与生物活性研究进展[J]. 实用肝脏病杂志,2005,8(5):307-310. doi: 10.3969/j.issn.1672-5069.2005.05.033
    [10] D Nogales,Da Lightner. On the structure of bilirubin in solution. 13C[1H] heteronuclear Overhauser effect NMR analyses in aqueous buffer and organic solvents[J]. J Biol Chem,1995,270(1):73-77. doi: 10.1074/jbc.270.1.73
    [11] 何凯. 血清胆红素在慢性心力衰竭的研究进展[J]. 检验医学与临床,2018,15(19):2984-2987. doi: 10.3969/j.issn.1672-9455.2018.19.045
    [12] Haruna Takao, Kei Hirabayashi, Yuki Nishigaya, et al. A substrate-bound structure of cyanobacterial biliverdin reductase identififies stacked substrates as critical for activity[J]. Nat Commun, 2017, 8期号: 14397.

    Haruna Takao,Kei Hirabayashi,Yuki Nishigaya,et al. A substrate-bound structure of cyanobacterial biliverdin reductase identififies stacked substrates as critical for activity[J]. Nat Commun,2017,8:14397.
    [13] 池肇春. 血红素加氧酶和胆绿素还原酶反应化学研究进展[J]. 中西医结合肝病杂志,2021,31(7):582-585.
    [14] Antony F. McDonagh. The biliverdin–bilirubin antioxidant cycle of cellular protection:Missing a wheel?[J]. Free Radic Biol Med,2010,49(5):814-820. doi: 10.1016/j.freeradbiomed.2010.06.001
    [15] Joon Nam,Yonghyun Lee,Yejin Yang,et al. Is it worth expending energy to convert biliverdin into bilirubin?[J]. Free Radic Biol Med,2018,124:232-240. doi: 10.1016/j.freeradbiomed.2018.06.010
    [16] 周阳,刘慧,张华,等. 胆绿素还原酶在抗肿瘤治疗中作用的研究进展[J]. 癌症进展,2020,18(8):757-760.
    [17] Sang Jin Kim,Min Jea Shin,Dae Won Kim,et al. Tat-biliverdin reductase a exerts a protective role in oxidative stress-induced hippocampal neuronal cell damage by regulating the apoptosis and MAPK signaling[J]. Int J Mol Sci,2020,21(8):2672. doi: 10.3390/ijms21082672
    [18] Thomas Jansen,Andreas Daiber. Direct antioxidant properties of bilirubin and biliverdin. Is there a role for biliverdin reductase?[J]. Front Pharmacol,2012,3:30.
    [19] Cesare Mancuso,Pina Guido,Marzia Perluigi,et al. Inhibition of lipid peroxidation and protein oxidation by endogenous and exogenous antioxidants in rat brain microsomes in vitro[J]. Neurosci Lett,2012,518(2):101-105. doi: 10.1016/j.neulet.2012.04.062
    [20] 刘颖迪,柏冰雪,任静,等. 外源性胆绿素对中波紫外线诱导的HaCaT细胞光损伤的保护作用[J]. 中华皮肤科杂志,2018,51(4):279-284. doi: 10.3760/cma.j.issn.0412-4030.2018.04.008
    [21] Manish Mishra,Joseph Fomusi Ndisang. A critical and comprehensive insight on heme oxygenase and related products including carbon monoxide,bilirubin,biliverdin and ferritin in type-1 and type-2 diabetes[J]. Curr Pharm Des,2014,20(9):1370-1391. doi: 10.2174/13816128113199990559
    [22] 王娟,周华成,薄玉龙,等. 胆绿素对脑死亡致大鼠肺损伤的影响[J]. 中华麻醉学杂志,2010,30(5):615-618. doi: 10.3760/cma.j.issn.0254-1416.2010.05.032
    [23] Chirag Vasavda,Ruchita Kotharia,Adarsha P,et al. Bilirubin links heme metabolism to neuroprotection by scavenging superoxide[J]. Cell Chem Biol,2019,26(10):1450-1460. doi: 10.1016/j.chembiol.2019.07.006
    [24] Maria J Monte,Elisa Lozano,Maria A,et al. Protective role of biliverdin against bile acid-induced oxidative stress in liver cells[J]. Free Radic Biol Med,2016,97:466-477. doi: 10.1016/j.freeradbiomed.2016.06.016
    [25] 张晓卉,林芳,马良娟. 外源性胆绿素对中波紫外线诱导的角质形成细胞光损伤的保护作用和机制[J]. 中华皮肤科杂志,2020,53(10):807-810.
    [26] Bingxue Bai, Yingdi Liu, Yan You, et al. Intraperitoneally administered biliverdin protects against UVB-induced skin photo-damage in hairless mice[J]. J Photochem PhotobiolB, 2015, 144期号: 35-41.

    Bingxue Bai,Yingdi Liu,Yan You,et al. Intraperitoneally administered biliverdin protects against UVB-induced skin photo-damage in hairless mice[J]. J Photochem PhotobiolB,2015,144:35-41.
    [27] 龚睿,蒋磊,宋宁,等. 胆绿素对脂多糖诱导小鼠RAW264.7巨噬细胞NLRP3炎性体激活的作用[J]. 医学研究杂志,2017,46(10):35-39. doi: 10.11969/j.issn.1673-548X.2017.10.010
    [28] Yiting Zhang,Yan Ding,Tai Lu,et al. Biliverdin reductase-A attenuated GMH induced inflammatory response in the spleen by inhibiting toll-like receptor-4 through eNOS/NO pathway[J]. J Neuroinflammation,2018,15(1):118. doi: 10.1186/s12974-018-1155-z
    [29] Barbara Andria,Adele Bracco,Chiara Attanasio,et al. Biliverdin protects against liver ischemia reperfusion injury in swine[J]. PLoS One,2013,8(7):e69972. doi: 10.1371/journal.pone.0069972
    [30] Wenfang Tian,Ping Weng,Qiong Sheng,et al. Biliverdin protects the isolated rat lungs from ischemia-reperfusion injury via antioxidative,anti-inflammatory and anti-apoptotic effects[J]. Chin Med J (Engl),2017,130(7):859-865. doi: 10.4103/0366-6999.202735
    [31] Junjie Li,Zhiyao Zou,Jia Liu,et al. Biliverdin administration ameliorates cerebral ischemia reperfusion injury in rats and is associated with proinflammatory factor downregulation[J]. Exp Ther Med,2017,14(1):671-679. doi: 10.3892/etm.2017.4549
    [32] 罗靖,高娴玲,邵建林,等. 胆绿素改善大鼠脑缺血再灌注损伤的作用机制[J]. 昆明医科大学学报,2020,41(11):1-6.
    [33] Zhiyao Zou,Jia Liu,Cheng Chang,et al. Biliverdin administration regulates the microRNA-mRNA expressional network associated with neuroprotection in cerebral ischemia reperfusion injury in rats[J]. Int J Mol Med,2019,43(3):1356-1372.
    [34] Kavita Bisht,Barbara Wegie,Jens Tampe,et al. Biliverdin modulates the expression of C5aR in response to endotoxin in part via mTOR signaling[J]. Biochem Biophys Res Commun,2014,449(1):94-99. doi: 10.1016/j.bbrc.2014.04.150
    [35] Hellíada Vasconcelos Chaves,Danielle Rocha do Val,Kátia Alves Ribeiro,et al. Heme oxygenase-1/biliverdin/carbon monoxide pathway downregulates hypernociception in rats by a mechanism dependent on cGMP/ATP-sensitive K+ channels[J]. Inflamm Res,2018,67(5):407-422. doi: 10.1007/s00011-018-1133-z
    [36] ShareeA Badseo,NicoleK Campbell,LouiseM Sullivan,et al. Suppression of human alloreactive T cells by linear tetrapyrroles; relevance for transplantation[J]. Transl Res,2016,178:81-94. doi: 10.1016/j.trsl.2016.07.011
    [37] Ferenc Zsila,György Mády. Biliverdin is the endogenous ligand of human serum α1-acid glycoprotein[J]. Biochem Biophys Res Commun,2008,372(3):503-507. doi: 10.1016/j.bbrc.2008.05.090
    [38] Ryan G Shiels,Wenu Hewage,Evan N,et al. Biliverdin and bilirubin sulfonate inhibit monosodium urate induced sterile inflammation in the rat[J]. Eur J Pharm Sci,2020,155:105546. doi: 10.1016/j.ejps.2020.105546
    [39] M Bonelli,A. Savitskaya,CW. Steiner,et al. Heme oxygenase-1 end products carbon monoxide and biliverdin ameliorate murine collagen induced arthritis[J]. Clin Exp Rheumatol,2012,30(1):73-78.
    [40] Melissa P Homsher,Michael T Astor,Michael W Butler. Immune challenges decrease biliverdin concentration in the spleen of northern Bobwhite quail,Colinus virginianus[J]. J Comp Physiol B,2018,188(3):505-515. doi: 10.1007/s00360-018-1146-5
    [41] Jessica L Baylor,Michael W Butler. Immune challenge-induced oxidative damage may be mitigated by biliverdin[J]. J Exp Biol,2019,222(Pt 6):jeb200055.
    [42] 魏刚. 血红素氧合酶-1抗动脉粥样硬化作用与机制的研究进展[J]. 心血管病学进展,2018,39(1):79-83.
    [43] Atsunori Nakao,Noriko Murase,Chien Ho,et al. Biliverdin administration prevents the formation of intimal hyperplasia induced by vascular injury[J]. Circulation,2005,112(4):587-591. doi: 10.1161/CIRCULATIONAHA.104.509778
    [44] Thomas Jansen,Marcus Hortmann,Matthias Oelze,et al. Conversion of biliverdin to bilirubin by biliverdin reductase contributes to endothelial cell protection by heme oxygenase-1 evidence for direct and indirect antioxidant actions of bilirubin[J]. J Mol Cell Cardiol,2010,49(2):186-195. doi: 10.1016/j.yjmcc.2010.04.011
    [45] J. A. Moraes,P. Barcellos-de-Souza,G. Rodrigues,et al. Heme modulates smooth muscle cell proliferation and migration via NADPH oxidase:A counter-regulatory role for heme oxygenase system[J]. Atherosclerosis,2012,224(2):394-400. doi: 10.1016/j.atherosclerosis.2012.07.043
    [46] J Zheng,Da Nagda,Sa Lajud,et al. Biliverdin’s regulation of reactive oxygen species signalling leads to potent inhibition of proliferative and angiogenic pathways in head and neck cancer[J]. Br J Cancer,2014,110(8):2116-2122. doi: 10.1038/bjc.2014.98
    [47] David Stucki,Julia Steinhausen,Philipp Westhof,et al. Endogenous Carbon Monoxide Signaling Modulates Mitochondrial Function and Intracellular Glucose Utilization:Impact of the Heme Oxygenase Substrate Hemin[J]. Antioxidants (Basel),2020,9(8):652. doi: 10.3390/antiox9080652
    [48] Qian Lv,Ying Yao,Wei Wang,et al. Biliverdin protects against cisplatin-induced apoptosis of renal tubular epithelial cells[J]. Huazhong Univ Sci Technolog Med Sci,2016,36(1):48-52. doi: 10.1007/s11596-016-1540-8
    [49] 孙洁芸,张鹏,杨欣颖,等. 胆绿素通过抗凋亡发挥对离体肺缺血/再灌注损伤的保护作用[J]. 中华危重病急救医学,2017,29(1):25-29.
    [50] Junjie Li,Lijia Peng,Wenya Bai,et al. Biliverdin protects against cerebral ischemia/reperfusion injury by regulating the miR-27a-3p/Rgs1 axis[J]. Neuropsychiatr Dis Treat,2021,22(17):1165-1181.
    [51] Aleš Berlec,Borut Štrukelj. A high-throughput biliverdin assay using infrared fluorescence[J]. J Vet Diagn Invest,2014,26(4):521-526. doi: 10.1177/1040638714535403
    [52] Mitja Martelanc,Lovro Žiberna,Sabina Passamonti,et al. Application of high-performance liquid chromatography combined with ultra-sensitive thermal lens spectrometric detection for simultaneous biliverdin and bilirubin assessment at trace levels in human serum[J]. Talanta,2016,154:92-98. doi: 10.1016/j.talanta.2016.03.053
    [53] Milena S. Dimitrijević,Jelena Bogdanović Pristov,Milan Žižić,et al. Biliverdin-copper complex at physiological pH[J]. Dalton Trans,2019,8(18):6061-6070.
    [54] Ruirui Xing,Qianli Zou,Chengqian Yuan,et al. Self-assembling endogenous biliverdin as a versatile near-infrared photothermal nanoagent for cancer theranostics[J]. Adv Mater,2019,31(16):e1900822. doi: 10.1002/adma.201900822
    [55] Parinaz Fathi,Hailey J Knox,Dinabandhu Sar,et al. Biodegradable biliverdin nanoparticles for efficient photoacoustic imaging[J]. ACS Nano,2019,13(7):7690-7704. doi: 10.1021/acsnano.9b01201
  • [1] 谭莹, 秦海燕, 孙翔, 苏彦伊, 王英宝.  丙泊酚调节MPP+诱导的SH-SY5Y细胞线粒体氧化应激和凋亡, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20240305
    [2] 董丽, 孙士波, 孙曙光.  灯盏花乙素抗氧化应激机制在防治心脑血管疾病中的研究进展, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20220423
    [3] 李俊杰, 蒋海燕, 白文娅, 霍思颖, 孙志生, 邵建林.  沉默RND3表达对氧糖缺失/复氧复糖损伤海马神经细胞炎症反应和细胞凋亡的影响, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20211012
    [4] 罗靖, 高娴玲, 邵建林, 张超, 张琦.  胆绿素改善大鼠脑缺血再灌注损伤的作用机制, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20201107
    [5] 郭安利, 付昌碧, 杨晓晴, 张士梅, 石正娟.  急性脑梗死患者肺部感染对氧化应激与炎性应激的影响, 昆明医科大学学报.
    [6] 曾庆菊, 李慧, 王晋文.  褪黑素对糖尿病大鼠氧化应激及足细胞凋亡的影响及作用机制, 昆明医科大学学报.
    [7] 戴青里, 孙贵虎, 闫斌, 郭涛, 戴青原.  过氧化氢诱导HUVECs氧化应激模型的构建, 昆明医科大学学报.
    [8] 曾柏瑞.  甲基苯丙胺与HIV-Tat蛋白协同改变大鼠血脑屏障通透性的氧化应激作用机制, 昆明医科大学学报.
    [9] 潘艳丽.  吡格列酮对高糖诱导下血管内皮细胞凋亡的影响, 昆明医科大学学报.
    [10] 张健.  盐霉素对人骨肉瘤MG-63细胞体外增殖和凋亡的影响, 昆明医科大学学报.
    [11] 边海霞.  单纯疱疹病毒性角膜炎抗氧化治疗的临床观察, 昆明医科大学学报.
    [12] 刘松.  1 800 MHz电磁波对大鼠心肌氧化应激的影响, 昆明医科大学学报.
    [13] 丁艳杰.  类风湿合并颈动脉硬化患者血清氧化应激状态与MMPs相关性分析, 昆明医科大学学报.
    [14] 张媛.  1 800 MHz电磁辐射对大鼠皮肤组织氧化应激的影响, 昆明医科大学学报.
    [15] 孙海梅.  缺血后处理对猪非梗死区心肌细胞凋亡的影响, 昆明医科大学学报.
    [16] 闫庆峰.  木犀草素对冷保存大鼠心脏心功能及氧化应激反应的影响, 昆明医科大学学报.
    [17] 李昆仑.  RNAi抑制Survivin基因的表达对乳腺癌SKBr-3细胞的影响, 昆明医科大学学报.
    [18] 赵学英.  p53基因在内质网应激诱导的晶状体上皮细胞凋亡中的作用, 昆明医科大学学报.
    [19] 桂莉.  2型糖尿病大鼠骨骼肌氧化应激与胰岛素抵抗的关系, 昆明医科大学学报.
    [20] 李国栋.  七叶皂甙钠抗大鼠视网膜缺血-再灌注后视网膜细胞凋亡的保护作用, 昆明医科大学学报.
  • 加载中
图(2)
计量
  • 文章访问数:  3763
  • HTML全文浏览量:  2221
  • PDF下载量:  58
  • 被引次数: 0
出版历程
  • 收稿日期:  2022-03-13
  • 刊出日期:  2022-06-25

目录

    /

    返回文章
    返回