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

应中央军委要求,2022年9月起,《药学实践杂志》将更名为《药学实践与服务》,双月刊,正文96页;2023年1月起,拟出版月刊,正文64页,数据库收录情况与原《药学实践杂志》相同。欢迎作者踊跃投稿!

炎症小体介导的细胞焦亡在非酒精性脂肪肝病中的作用及机制

张文杰 孙迪阳 王培

张文杰, 孙迪阳, 王培. 炎症小体介导的细胞焦亡在非酒精性脂肪肝病中的作用及机制[J]. 药学实践与服务, 2020, 38(1): 9-13,41. doi: 10.3969/j.issn.1006-0111.201902051
引用本文: 张文杰, 孙迪阳, 王培. 炎症小体介导的细胞焦亡在非酒精性脂肪肝病中的作用及机制[J]. 药学实践与服务, 2020, 38(1): 9-13,41. doi: 10.3969/j.issn.1006-0111.201902051
ZHANG Wenjie, SUN Diyang, WANG Pei. The role and mechanism of inflammasome-associated pyroptosis in nonalcoholic fatty liver disease[J]. Journal of Pharmaceutical Practice and Service, 2020, 38(1): 9-13,41. doi: 10.3969/j.issn.1006-0111.201902051
Citation: ZHANG Wenjie, SUN Diyang, WANG Pei. The role and mechanism of inflammasome-associated pyroptosis in nonalcoholic fatty liver disease[J]. Journal of Pharmaceutical Practice and Service, 2020, 38(1): 9-13,41. doi: 10.3969/j.issn.1006-0111.201902051

炎症小体介导的细胞焦亡在非酒精性脂肪肝病中的作用及机制

doi: 10.3969/j.issn.1006-0111.201902051

The role and mechanism of inflammasome-associated pyroptosis in nonalcoholic fatty liver disease

  • 摘要: 非酒精性脂肪肝病包含单纯性脂肪肝、非酒精性脂肪肝炎和肝硬化等一系列病变,是造成肝硬化、肝细胞癌症的主要因素和肝脏器官移植的重要诱因。非酒精性脂肪肝的发病机制尚不明确,除了加强运动、改善饮食习惯外,目前尚无公认有效的药物治疗方式。细胞焦亡是一种新发现的程序性细胞死亡方式,依赖于天冬氨酸特异性半胱氨酸蛋白酶1(caspase-1)或caspase-11等介导的炎性小体的激活。细胞焦亡过程中常伴有炎症反应的发生,而炎症小体则是细胞产生焦亡和炎症反应所必需的多聚体蛋白复合物,其主要功能是活化caspase-1,从而间接调控炎症因子白介素1(IL-1)和IL-18的表达和分泌。最近的研究表明,细胞焦亡和炎症小体在非酒精性脂肪肝病的发生发展中起重要作用。针对该领域的最新研究进行综述,以期为非酒精性脂肪肝的防治提供新的科学认识和信息。
  • [1] VILLANUEVA M T. Conscious uncoupling in NASH[J]. Nat Rev Drug Discov,2017,16(4):239
    [2] NEUSCHWANDER-TETRI B A. Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: The central role of nontriglyceride fatty acid metabolites[J]. Hepatology,2010,52(2):774-788
    [3] MARRA F, SVEGLIATI-BARONI G. Lipotoxicity and the gut-liver axis in NASH pathogenesis[J]. J Hepatol,2018,68(2):280-295
    [4] PEVERILL W, POWELL L, SKOIEN R. Evolving concepts in the pathogenesis of NASH: beyond steatosis and inflammation[J]. Int J Mol Sci,2014,15(5):8591-8638
    [5] LAZIC M, INZAUGARAT M E, POVERO D, et al. Reduced dietary omega-6 to omega-3 fatty acid ratio and 12/15-lipoxygenase deficiency are protective against chronic high fat diet-induced steatohepatitis[J]. Plos One,2014,9(9):e107658
    [6] ABDELMALEK M F, SUZUKI A, GUY C, et al. Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease[J]. Hepatology,2010,51(6):1961-1971
    [7] IOANNOU G N, VAN ROOYEN D M, SAVARD C, et al. Cholesterol-lowering drugs cause dissolution of cholesterol crystals and disperse Kupffer cell crown-like structures during resolution of NASH[J]. J Lipid Res,2015,56(2):277-285
    [8] MIELE L C, MARRONE G, LAURITANO C, et al. Gut-liver axis and microbiota in NAFLD: insight pathophysiology for novel therapeutic target[J]. Curr Pharm Des,2013,19(29):5314-5324
    [9] SCHRODER K, TSCHOPP J. The inflammasomes[J]. Cell,2010,140(6):821-832
    [10] MINKIEWICZ J, DE RIVERO VACCARI J P, KEANE R W. Human astrocytes express a novel NLRP2 inflammasome[J]. Glia,2013,61(7):1113-1121
    [11] Wlodarska M, Thaiss CA, Nowarski R, et al. NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion[J]. Cell,2014,156(5):1045-1059
    [12] OHASHI K, WANG Z J, YANG Y M, et al. NOD-like receptor C4 inflammasome regulates the growth of colon cancer liver metastasis in NAFLD[J]. Hepatology,2019:30693
    [13] DING J J, WANG K, LIU W, et al. Pore-forming activity and structural autoinhibition of the gasdermin family[J]. Nature,2016,535(7610):111-116
    [14] WREE A, MCGEOUGH M D, PEÑA C A, et al. NLRP3 inflammasome activation is required for fibrosis development in NAFLD[J]. J Mol Med,2014,92(10):1069-1082
    [15] MATSUZAKA T, ATSUMI A, MATSUMORI R, et al. Elovl6 promotes nonalcoholic steatohepatitis[J]. Hepatology,2012,56(6):2199-2208
    [16] WEN H T, GRIS D, LEI Y, et al. Fatty acid–induced NLRP3-ASC inflammasome activation interferes with insulin signaling[J]. Nat Immunol,2011,12(5):408-415
    [17] WREE A, EGUCHI A, MCGEOUGH M D, et al. NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice[J]. Hepatology,2014,59(3):898-910
    [18] MRIDHA A R, WREE A, ROBERTSON A A B, et al. NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice[J]. J Hepatol,2017,66(5):1037-1046
    [19] YANG S J, LIM Y. Resveratrol ameliorates hepatic metaflammation and inhibits NLRP3 inflammasome activation[J]. Metabolism,2014,63(5):693-701
    [20] XU B, JIANG M, CHU Y, et al. Gasdermin D plays a key role as a pyroptosis executor of non-alcoholic steatohepatitis in humans and mice[J]. J Hepatol,2018,68(4):773-782
    [21] MIURA K, KODAMA Y, INOKUCHI S, et al. Toll-like receptor 9 promotes steatohepatitis by induction of interleukin-1β in mice[J]. Gastroenterology,2010,139(1):323-334.e7
    [22] STIENSTRA R, SAUDALE F, DUVAL C, et al. Kupffer cells promote hepatic steatosis via interleukin-1β-dependent suppression of peroxisome proliferator-activated receptor α activity[J]. Hepatology,2010,51(2):511-522
    [23] VANDANMAGSAR B, YOUM Y, RAVUSSIN A, et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance[J]. Nat Med,2011,17(2):179-188
    [24] PETRASEK J, BALA S S, CSAK T, et al. IL-1 receptor antagonist ameliorates inflammasome-dependent alcoholic steatohepatitis in mice[J]. J Clin Invest,2012,122(10):3476-3489
    [25] WITEK R P, STONE W C, KARACA F G, et al. Pan-caspase inhibitor VX-166 reduces fibrosis in an animal model of nonalcoholic steatohepatitis[J]. Hepatology,2009,50(5):1421-1430
    [26] KIM S H, KIM G, HAN D H, et al. Ezetimibe ameliorates steatohepatitis via AMP activated protein kinase-TFEB-mediated activation of autophagy and NLRP3 inflammasome inhibition[J]. Autophagy,2017,13(10):1767-1781
    [27] HENAO-MEJIA J, ELINAV E, JIN C C, et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity[J]. Nature,2012,482(7384):179-185
    [28] DE MINICIS S, RYCHLICKI C, AGOSTINELLI L, et al. Dysbiosis contributes to fibrogenesis in the course of chronic liver injury in mice[J]. Hepatology,2014,59(5):1738-1749
    [29] CSAK T, PILLAI A, GANZ M, et al. Both bone marrow-derived and non-bone marrow-derived cells contribute to AIM2 and NLRP3 inflammasome activation in a MyD88-dependent manner in dietary steatohepatitis[J]. Liver Int,2014,34(9):1402-1413
    [30] MURPHY A J, KRAAKMAN M J, KAMMOUN H L, et al. IL-18 production from the NLRP1 inflammasome prevents obesity and metabolic syndrome[J]. Cell Metab,2016,23(1):155-164
    [31] ANITHA M, REICHARDT F, TABATABAVAKILI S, et al. Intestinal dysbiosis contributes to the delayed gastrointestinal transit in high-fat diet fed mice[J]. Cell Mol Gastroenterol Hepatol,2016,2(3):328-339
    [32] CHEN G Y, LIU M C, WANG F Y, et al. A functional role for Nlrp6 in intestinal inflammation and tumorigenesis[J]. J Immunol,2011,186(12):7187-7194
    [33] ZHANG Q, RAOOF M, CHEN Y, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury[J]. Nature,2010,464(7285):104-107
    [34] SUN Q, LOUGHRAN P, SHAPIRO R, et al. Redox-dependent regulation of hepatocyte absent in melanoma 2 inflammasome activation in sterile liver injury in mice[J]. Hepatology,2017,65(1):253-268
    [35] WATANABE A, SOHAIL M A, GOMES D A, et al. Inflammasome-mediated regulation of hepatic stellate cells[J]. Am J Physiol Gastrointest Liver Physiol,2009,296(6):G1248-G1257
    [36] WREE A, MCGEOUGH M D, INZAUGARAT M E, et al. NLRP3 inflammasome driven liver injury and fibrosis: Roles of IL-17 and TNF in mice[J]. Hepatology,2018,67(2):736-749
  • [1] 李锐, 张倩倩, 王瑞冬, 高小峰.  国家集中带量采购政策下样本医院良性前列腺增生治疗药物使用情况分析 . 药学实践与服务, 2025, 43(2): 1-6. doi: 10.12206/j.issn.2097-2024.202408031
    [2] 杨念, 张博乐, 张俊霞, 张振强.  一种中药组合物对ANIT诱导的小鼠胆汁淤积肝损伤的保护作用研究 . 药学实践与服务, 2024, 42(12): 508-511, 519. doi: 10.12206/j.issn.2097-2024.202305008
    [3] 冯志惠, 邓仪卿, 叶冰, 安培, 张宏, 张海军.  雀梅藤石油醚提取物诱导三阴性乳腺癌细胞凋亡的实验研究 . 药学实践与服务, 2024, 42(6): 253-259. doi: 10.12206/j.issn.2097-2024.202311055
    [4] 夏哲炜, 曾垣烨, 朱海菲, 李育, 陈啸飞.  核磁共振磷谱法测定磷酸氢钙咀嚼片中药物含量 . 药学实践与服务, 2024, 42(9): 399-401, 406. doi: 10.12206/j.issn.2097-2024.202404063
    [5] 陈怡君, 王卓, 何苗, 张宇, 田泾.  泌尿系统碎石术抗菌药物预防使用合理管控实践 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202402034
    [6] 姜涛, 徐卫凡, 蒋益萍, 夏天爽, 辛海量.  巴戟天丸组方对Aβ损伤成骨细胞的作用及基于网络药理学的机制研究 . 药学实践与服务, 2024, 42(7): 285-290, 296. doi: 10.12206/j.issn.2097-2024.202305011
    [7] 杨媛媛, 安晓强, 许佳捷, 江键, 梁媛媛.  正极性驻极体联合5-氟尿嘧啶对瘢痕成纤维细胞生长抑制的协同作用 . 药学实践与服务, 2024, 42(6): 244-247. doi: 10.12206/j.issn.2097-2024.202310027
    [8] 张元林, 宋凯, 孙蕊, 舒飞, 舒丽芯, 杨樟卫.  基于真实世界数据的药物利用研究综述 . 药学实践与服务, 2024, 42(6): 238-243. doi: 10.12206/j.issn.2097-2024.202312010
    [9] 张晶晶, 索丽娜, 郑兆红.  89例细菌性肝脓肿的临床特征及抗感染治疗分析 . 药学实践与服务, 2024, 42(6): 267-272. doi: 10.12206/j.issn.2097-2024.202302039
    [10] 张艺昕, 关欣怡, 王博宁, 闻俊, 洪战英.  二氢吡啶类钙离子拮抗药物手性分析及其立体选择性药动学研究进展 . 药学实践与服务, 2024, 42(8): 319-324. doi: 10.12206/j.issn.2097-2024.202308062
    [11] 迟文雅, 袁艳, 李伟林, 吴茼妤, 俞媛.  负载骨髓间充质干细胞/白藜芦醇脂质体的水凝胶支架用于创伤性脑损伤治疗 . 药学实践与服务, 2024, 42(): 1-8. doi: 10.12206/j.issn.2097-2024.202406034
    [12] 何亚伦, 祁智, 常杰.  消胀通便膏在晚期肝癌患者阿片类药物相关性便秘中的应用研究 . 药学实践与服务, 2024, 42(12): 520-523. doi: 10.12206/j.issn.2097-2024.202309009
    [13] 修建平, 杨朝爱, 刘禧澳, 潘乾禹, 韦广旭, 王卫星.  全反式维甲酸对肝星状细胞活化及氧化应激的作用和机制探索 . 药学实践与服务, 2024, 42(7): 291-296. doi: 10.12206/j.issn.2097-2024.202312054
    [14] 张岩, 李炎君, 刘家荟, 邓娇, 原苑, 张敬一.  药物性肝损伤不良反应分析 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202404034
    [15] 李想, 陆鸿远, 张明玉, 高欢, 姚东, 许子华.  米格列醇激活UCP1介导棕色脂肪对冷暴露小鼠损伤的研究 . 药学实践与服务, 2024, 42(): 1-6. doi: 10.12206/j.issn.2097-2024.202404005
    [16] 刘丽艳, 余小翠, 孙传铎.  纳武利尤单抗治疗非小细胞肺癌有效性及安全性的Meta分析 . 药学实践与服务, 2024, 42(10): 451-456. doi: 10.12206/j.issn.2097-2024.202310044
    [17] 孙丹倪, 黄勇, 张嘉宝, 王培.  代谢相关脂肪性肝病的无创诊断与药物治疗 . 药学实践与服务, 2024, 42(10): 411-418. doi: 10.12206/j.issn.2097-2024.202403049
    [18] 宋雨桐, 夏德润, 顾珩, 唐少文, 易洪刚, 沃红梅.  帕博利珠单抗与铂类化疗方案在晚期非小细胞肺癌一线治疗中的药物经济学评价 . 药学实践与服务, 2024, 42(8): 334-340. doi: 10.12206/j.issn.2097-2024.202303023
    [19] 杨嘉宁, 赵一颖, 肖伟.  七味脂肝方对非酒精性脂肪性肝炎动物模型的药效学评价 . 药学实践与服务, 2024, 42(9): 389-398. doi: 10.12206/j.issn.2097-2024.202404096
    [20] 岳春华, 贲永光, 王海桥.  基于NLRP1炎症小体探讨百合知母汤抗抑郁的作用机制 . 药学实践与服务, 2024, 42(8): 325-333. doi: 10.12206/j.issn.2097-2024.202401033
  • 加载中
计量
  • 文章访问数:  5322
  • HTML全文浏览量:  606
  • PDF下载量:  3404
  • 被引次数: 0
出版历程
  • 收稿日期:  2019-02-22
  • 修回日期:  2019-07-18

炎症小体介导的细胞焦亡在非酒精性脂肪肝病中的作用及机制

doi: 10.3969/j.issn.1006-0111.201902051

摘要: 非酒精性脂肪肝病包含单纯性脂肪肝、非酒精性脂肪肝炎和肝硬化等一系列病变,是造成肝硬化、肝细胞癌症的主要因素和肝脏器官移植的重要诱因。非酒精性脂肪肝的发病机制尚不明确,除了加强运动、改善饮食习惯外,目前尚无公认有效的药物治疗方式。细胞焦亡是一种新发现的程序性细胞死亡方式,依赖于天冬氨酸特异性半胱氨酸蛋白酶1(caspase-1)或caspase-11等介导的炎性小体的激活。细胞焦亡过程中常伴有炎症反应的发生,而炎症小体则是细胞产生焦亡和炎症反应所必需的多聚体蛋白复合物,其主要功能是活化caspase-1,从而间接调控炎症因子白介素1(IL-1)和IL-18的表达和分泌。最近的研究表明,细胞焦亡和炎症小体在非酒精性脂肪肝病的发生发展中起重要作用。针对该领域的最新研究进行综述,以期为非酒精性脂肪肝的防治提供新的科学认识和信息。

English Abstract

张文杰, 孙迪阳, 王培. 炎症小体介导的细胞焦亡在非酒精性脂肪肝病中的作用及机制[J]. 药学实践与服务, 2020, 38(1): 9-13,41. doi: 10.3969/j.issn.1006-0111.201902051
引用本文: 张文杰, 孙迪阳, 王培. 炎症小体介导的细胞焦亡在非酒精性脂肪肝病中的作用及机制[J]. 药学实践与服务, 2020, 38(1): 9-13,41. doi: 10.3969/j.issn.1006-0111.201902051
ZHANG Wenjie, SUN Diyang, WANG Pei. The role and mechanism of inflammasome-associated pyroptosis in nonalcoholic fatty liver disease[J]. Journal of Pharmaceutical Practice and Service, 2020, 38(1): 9-13,41. doi: 10.3969/j.issn.1006-0111.201902051
Citation: ZHANG Wenjie, SUN Diyang, WANG Pei. The role and mechanism of inflammasome-associated pyroptosis in nonalcoholic fatty liver disease[J]. Journal of Pharmaceutical Practice and Service, 2020, 38(1): 9-13,41. doi: 10.3969/j.issn.1006-0111.201902051
参考文献 (36)

目录

    /

    返回文章
    返回