脓毒症诱发肝损伤的发病机制研究进展

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摘要脓毒症是一种威胁生命的急性综合征，也是重症监护室患者死亡的主要原因。肝脏维持着人体代谢和免疫平衡，脓毒症时发生的肝损伤往往预示着不良预后和住院死亡率升高。近年来大量研究表明炎症级联反应、细胞焦亡、氧化应激、自噬、miRNA等因素在脓毒症肝损伤的发生过程中起着重要作用。本文综述了近年来脓毒症诱发肝损伤的发病机制，以期为寻找有效治疗靶点提供新思路。

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	陈文胜
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关键词 ：脓毒症, 肝损伤, 细胞焦亡, 氧化应激, 自噬, miRNA, 信号通路, 炎症反应

收稿日期: 2022-07-22

基金资助:吴阶平医学基金会临床科研专项资助基金（320.6750.2022-02-20）

通讯作者: 刘文明（通讯作者），主任医师，硕士生导师，E-mail lwmicu@163.com

作者简介: 陈文胜（1995—），男，硕士研究生；

引用本文:

陈文胜，刘文明. 脓毒症诱发肝损伤的发病机制研究进展[J]. 江苏大学学报:医学版, 2023, 33(02): 112-117.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2023/V33/I02/112

［1］Minasyan H. Sepsis: mechanisms of bacterial injury to the patient［J］. Scand J Trauma Resusc Emerg Med, 2019, 27(1): 19.
［2］Woz＇nica EA, Inglot M, Woz＇nica RK, et al. Liver dysfunction in sepsis［J］. Adv Clin Exp Med, 2018, 27(4): 547-551.
［3］Gaddam RR, Fraser R, Badiei A, et al. Differential effects of kupffer cell inactivation on inflammation and the liver sieve following caecalligation and punctureinduced sepsis in mice［J］. Shock, 2017, 47(4): 480-490.
［4］Wang H, Liu D. Baicalin inhibits highmobility group box 1 release and improves survival in experimental sepsis［J］. Shock, 2014, 41(4): 324-330.
［5］尹海燕, 邱敏珊, 何丹, 等. 姜黄素对脓毒症大鼠肝细胞的保护作用［J］. 中华危重病急救医学, 2017, 29(2): 162-166.
［6］Gao H, Cui Y, Kang N, et al. Isoacteoside, a dihydroxyphenylethyl glycoside, exhibits antiinflammatory effects through blocking tolllike receptor 4 dimerization［J］. Br J Pharmacol, 2017, 174(17): 2880-2896.
［7］何俊俐, 沈贵月, 刘安定, 等. FK866对脓毒症小鼠肝损伤的保护作用［J］. 中华危重病急救医学, 2018, 30(6): 583-587.
［8］Dogˇanyigˇit Z, Okan A, Kaymak E, et al. Investigation of protective effects of apilarnil against lipopolysaccharide induced liver injury in rats via TLR 4/ HMGB1/ NFκB pathway［J］. Biomed Pharmacother, 2020, 125: 109967.
［9］Wu J, Lin S, Wan B, et al. Pyroptosis in liver disease: new insights into disease mechanisms［J］. Aging Dis, 2019, 10(5): 1094-1108.
［10］Hong MK, Hu LL, Zhang YX, et al. 6Gingerol ameliorates sepsisinduced liver injury through the Nrf2 pathway［J］. Int Immunopharmacol, 2020, 80: 106196.
［11］Chen YL, Xu G, Liang X, et al. Inhibition of hepatic cells pyroptosis attenuates CLPinduced acute liver injury［J］. Am J Transl Res, 2016, 8(12): 5685-5695.
［12］Zhou R, Yazdi AS, Menu P, et al. A role for mitochondria in NLRP3 inflammasome activation［J］. Nature, 2011, 469(7329): 221-225.
［13］Li Z, Liu T, Feng Y, et al. PPARγ alleviates sepsisinduced liver injury by inhibiting hepatocyte pyroptosis via inhibition of the ROS/TXNIP/NLRP3 signaling pathway［J］. Oxid Med Cell Longev, 2022, 2022: 1269747.
［14］Cheng KT, Xiong S, Ye Z, et al. Caspase11mediated endothelial pyroptosis underlies endotoxemiainduced lung injury［J］. J Clin Invest, 2017, 127(11): 4124-4135.
［15］Rathinam VAK, Zhao Y, Shao F. Innate immunity to intracellular LPS［J］. Nat Immunol, 2019, 20(5): 527-533.
［16］Zhao YY, Wu DM, He M, et al. Samotolisib attenuates acute liver injury through inhibiting caspase11mediated pyroptosis via regulating E3 ubiquitin ligase Nedd4［J］. Front Pharmacol, 2021, 12: 726198.
［17］Liu J, Du S, Kong Q, et al. HSPA12A attenuates lipopolysaccharideinduced liver injury through inhibiting caspase11mediated hepatocyte pyroptosis via PGC1αdependent acyloxyacyl hydrolase expression［J］. Cell Death Differ, 2020, 27(9): 2651-2667.
［18］Rühl S, Broz P. Caspase11 activates a canonical NLRP3 inflammasome by promoting K+ efflux［J］. Eur J Immunol, 2015, 45(10): 2927-2936.
［19］Xu D, Liao S, Lv Y, et al. NMRbased metabolomics approach reveals effects of antioxidant nutrients in sepsisinduced changes in rat liver injury［J］. J Nutr Biochem, 2020, 85: 108440.
［20］Li L, Wang H, Zhao S, et al. Paeoniflorin ameliorates lipopolysaccharideinduced acute liver injury by inhibiting oxidative stress and inflammation via SIRT1/FOXO1a/SOD2 signaling in rats［J］. Phytother Res, 2022, 36(6): 2558-2571.
［21］Hwang YJ, Lee EW, Song J, et al. MafK positively regulates NFκB activity by enhancing CBPmediated p65 acetylation［J］. Sci Rep, 2013, 3: 3242.
［22］Dai JM, Guo WN, Tan YZ, et al. Wogonin alleviates liver injury in sepsis through Nrf2mediated NFκB signalling suppression［J］. J Cell Mol Med, 2021, 25(12): 5782-5798.
［23］Gao K, Niu J, Dang X. Neuroprotection of melatonin on spinal cord injury by activating autophagy and inhibiting apoptosis via SIRT1/AMPK signaling pathway［J］. Biotechnol Lett, 2020, 42(10): 2059-2069.
［24］Cantó C, GerhartHines Z, Feige JN, et al. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity［J］. Nature, 2009, 458(7241): 1056-1060.
［25］Sun Y, Xia M, Yan H, et al. Berberine attenuates hepatic steatosis and enhances energy expenditure in mice by inducing autophagy and fibroblast growth factor 21［J］. Br J Pharmacol, 2018, 175(2): 374-387.
［26］Yu Q, Zou L, Yuan X, et al. Dexmedetomidine protects against septic liver injury by enhancing autophagy through activation of the AMPK/SIRT1 signaling pathway［J］. Front Pharmacol, 2021, 12: 658677.
［27］Chen Z, Liu L, Cheng Q, et al. Mitochondrial E3 ligase MARCH5 regulates FUNDC1 to finetune hypoxic mitophagy［J］. EMBO Rep, 2017, 18(3): 495-509.
［28］Yan M, Yu Y, Mao X, et al. Hydrogen gas inhalation attenuates sepsisinduced liver injury in a FUNDC1dependent manner［J］. Int Immunopharmacol, 2019, 71: 61-67.
［29］Xue S, Zhou Y, Zhang J, et al. Anemoside B4 exerts anticancer effect by inducing apoptosis and autophagy through inhibition of PI3K/Akt/mTOR pathway in hepatocellular carcinoma［J］. Am J Transl Res, 2019, 11(4): 2580-2589.
［30］Pei L, He L. Hepatoprotective effect of anemoside B4 against sepsisinduced acute liver injury through modulating the mTOR/p70S6Kmediated autophagy［J］. Chem Biol Interact, 2021, 345: 109534.
［31］Cho HI, Kim SJ, Choi JW, et al. Genipin alleviates sepsisinduced liver injury by restoring autophagy［J］. Br J Pharmacol, 2016, 173(6): 980-991.
［32］Jiang Z, Bo L, Meng Y, et al. Overexpression of homeodomaininteracting protein kinase 2 (HIPK2) attenuates sepsismediated liver injury by restoring autophagy［J］. Cell Death Dis, 2018, 9(9): 847.
［33］Chen Z, Nie SD, Qu ML, et al. The autophagic degradation of Cav1 contributes to PAinduced apoptosis and inflammation of astrocytes［J］. Cell Death Dis, 2018, 9(7): 771.
［34］Li X, Liu F, Zhang X, et al. NotchHes1 axis controls TLR7mediated autophagic death of macrophage via induction of P62 in mice with lupus［J］. Cell Death Dis, 2016, 7(8): e2341.
［35］Xu Y, Li Y, Liu X, et al. SPIONs enhances IL10producing macrophages to relieve sepsis via Cav1Notch1/HES1mediated autophagy［J］. Int J Nanomedicine, 2019, 14: 6779-6797.
［36］Hu X, Deng J, Yu T, et al. ATF4 deficiency promotes intestinal inflammation in mice by reducing uptake of glutamine and expression of antimicrobial peptides［J］. Gastroenterology, 2019, 156(4): 1098-1111.
［37］Song S, Tan J, Miao Y, et al. Intermittenthypoxiainduced autophagy activation through the ERstressrelated PERK/eIF2α/ATF4 pathway is a protective response to pancreatic βcell apoptosis［J］. Cell Physiol Biochem, 2018, 51(6): 2955-2971.
［38］Shao L, Xiong X, Zhang Y, et al. IL22 ameliorates LPSinduced acute liver injury by autophagy activation through ATF4ATG7 signaling［J］. Cell Death Dis, 2020, 11(11): 970.
［39］何爱凤, 秦晓梦, 尹江宁, 等. 基于生物信息学分析miR30a及相关炎症指标在脓毒症中的表达及临床意义［J］. 江苏大学学报（医学版）, 2022, 32(2): 118-123.
［40］Chen L, Lu Q, Deng F, et al. miR103a3p could attenuate sepsisinduced liver injury by targeting HMGB1［J］. Inflammation, 2020, 43(6): 2075-2086.
［41］Zhou YP, Xia Q. Inhibition of miR103a3p suppresses lipopolysaccharideinduced sepsis and liver injury by regulating FBXW7 expression［J］. Cell Biol Int, 2020, 44(9): 1798-1810.
［42］Roderburg C, Benz F, Vargas Cardenas D, et al. Elevated miR122 serum levels are an independent marker of liver injury in inflammatory diseases［J］. Liver Int, 2015, 35(4): 1172-1184.
［43］Leelahavanichkul A, Somparn P, Panich T, et al. Serum miRNA122 in acute liver injury induced by kidney injury and sepsis in CD1 mouse models［J］. Hepatol Res, 2015, 45(13): 1341-1352.