淀粉样蛋白在肝脏中的生理病理作用

宗也凯; 刘江凯

doi:10.3969/j.issn.1001-5256.2023.11.031

淀粉样蛋白在肝脏中的生理病理作用

DOI: 10.3969/j.issn.1001-5256.2023.11.031

宗也凯¹,
刘江凯^2, , ,

1.
河南中医药大学第一临床医学院脾胃肝胆科，郑州 450008
2.
河南中医药大学第一附属医院脾胃肝胆科，郑州 450008

基金项目:

国家自然科学基金 (U1504825);

河南省中医药拔尖人才项目 (Yuwei TCM letter 2021-15)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：宗也凯负责论文设计，撰写论文；刘江凯参与论文指导。

详细信息

通信作者:
刘江凯， 13592553982@126.com （ORCID： 0000-0002-1529-5089）

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出版历程
- 收稿日期: 2023-02-07
- 录用日期: 2023-03-08
- 出版日期: 2023-11-28

The physiological and pathological role of amyloid protein in the liver

Yekai ZONG¹,
Jiangkai LIU^{2
, ,
,}

1.
Department of Hepatology and Spleen-Stomach，The First Clinical Medical College of Henan University of Chinese Medicine，Zhengzhou 450008，China
2.
Department of Hepatology and Spleen-Stomach，The First Affiliated Hospital of Henan University of Chinese Medicine，Zhengzhou 450008，China

Research funding:

National Natural Science Foundation of China (U1504825);

Henan TCM Top-notch Talent Program (Yuwei TCM letter 2021-15)

More Information

Corresponding author: LIU Jiangkai， 13592553982@126.com （ORCID： 0000-0002-1529-5089）

摘要

摘要: 淀粉样蛋白被用来描述因蛋白质错误折叠而形成的纤维状聚集体，它与一系列淀粉样变性疾病有关。当淀粉样蛋白沉积在肝脏，就会导致肝淀粉样变性，从而诱发相关病理改变影响肝脏正常生理功能，但这一疾病少有报道且临床常常被忽视。本文主要讨论了淀粉样蛋白在肝脏中的生理病理作用及机制，以便于加深对淀粉样蛋白相关疾病的理解并为相关研究和临床治疗提供一定参考。
- 淀粉样蛋白 /
- 淀粉样变性 /
- 肝疾病 /
- 病理过程
Abstract: Amyloid protein （AP） is used to describe the fibrous aggregates that form when proteins are misfolded， and it is associated with a series of amyloidosis diseases. When AP is deposited in the liver， it will lead to liver amyloidosis， thereby inducing related pathological changes that affect the normal physiological function of the liver； however， this disease is rarely reported and often neglected in clinical practice. This article reviews the physiological and pathological effects and mechanisms of AP in the liver， so as to improve the understanding of AP-related diseases and provide a reference for related research and clinical treatment.
- Amyloid /
- Amyloidosis /
- Liver Diseases /
- Pathologic Processes

HTML全文

表 1 不同器官淀粉样变性临床表现^［1］

Table 1. Clinical manifestations of amyloidosis in different organs^［1］

器官	应怀疑淀粉样变的临床体征和症状
肝	肝肿大，早饱，明显无意的体质量减轻，出血性疾病
心	呼吸短促，端坐呼吸，阵发性夜间呼吸困难，颈静脉扩张，外周水肿，心律失常
肾	外周水肿
胃肠道	排便习惯不规律，早饱，体质量减轻，胃肌轻瘫，吞咽困难，胃肠出血
周围神经	长度相关的对称周边神经病变，自主神经病变（勃起功能障碍、体位性高血压、排尿功能障碍、早饱、排便不规则习惯）

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参考文献(64)

[1]	VAXMAN I, GERTZ M. When to suspect a diagnosis of amyloidosis[J]. Acta Haematol, 2020, 143( 4): 304- 311. DOI: 10.1159/000506617.
[2]	STARON A, CONNORS LH, RUBERG FL, et al. A new era of amyloidosis: the trends at a major US referral centre[J]. Amyloid, 2019, 26( 4): 192- 196. DOI: 10.1080/13506129.2019.1640672.
[3]	DIAS E, CARDOSO H, MARQUES M, et al. Hepatic amyloidosis: a prevalence study and clinical characterization of a rare and severe disease[J]. Rev Esp Enferm Dig, 2023, 115( 1): 16- 21. DOI: 10.17235/reed.2022.8622/2022.
[4]	CHANDAN VS, SHAH SS, LAM-HIMLIN DM, et al. Globular hepatic amyloid is highly sensitive and specific for LECT2 amyloidosis[J]. Am J Surg Pathol, 2015, 39( 4): 558- 564. DOI: 10.1097/PAS.0000000000000373.
[5]	EISENBERG DS, SAWAYA MR. Structural studies of amyloid proteins at the molecular level[J]. Annu Rev Biochem, 2017, 86: 69- 95. DOI: 10.1146/annurev-biochem-061516-045104.
[6]	SAWAYA MR, SAMBASHIVAN S, NELSON R, et al. Atomic structures of amyloid cross-beta spines reveal varied steric zippers[J]. Nature, 2007, 447( 7143): 453- 457. DOI: 10.1038/nature05695.
[7]	RIEK R, EISENBERG DS. The activities of amyloids from a structural perspective[J]. Nature, 2016, 539( 7628): 227- 235. DOI: 10.1038/nature20416.
[8]	CHUANG E, HORI AM, HESKETH CD, et al. Amyloid assembly and disassembly[J]. J Cell Sci, 2018, 131( 8):jcs. 189928. DOI: 10.1242/jcs.189928.
[9]	BENSON MD, BUXBAUM JN, EISENBERG DS, et al. Amyloid nomenclature 2020: update and recommendations by the International Society of Amyloidosis(ISA) nomenclature committee[J]. Amyloid, 2020, 27( 4): 217- 222. DOI: 10.1080/13506129.2020.1835263.
[10]	SAWAYA MR, HUGHES MP, RODRIGUEZ JA, et al. The expanding amyloid family: Structure, stability, function, and pathogenesis[J]. Cell, 2021, 184( 19): 4857- 4873. DOI: 10.1016/j.cell.2021.08.013.
[11]	BENSON MD, BUXBAUM JN, EISENBERG DS, et al. Amyloid nomenclature 2018: recommendations by the International Society of Amyloidosis(ISA) nomenclature committee[J]. Amyloid, 2018, 25( 4): 215- 219. DOI: 10.1080/13506129.2018.1549825.
[12]	BUXBAUM JN, DISPENZIERI A, EISENBERG DS, et al. Amyloid nomenclature 2022: update, novel proteins, and recommendations by the International Society of Amyloidosis(ISA) Nomenclature Committee[J]. Amyloid, 2022, 29( 4): 213- 219. DOI: 10.1080/13506129.2022.2147636.
[13]	GIANNINI G, NAST CC. An organ system-based approach to differential diagnosis of amyloid type in surgical pathology[J]. Arch Pathol Lab Med, 2020, 144( 3): 379- 387. DOI: 10.5858/arpa.2018-0509-RA.
[14]	MEREUTA OM, THEIS JD, VRANA JA, et al. Leukocyte cell-derived chemotaxin 2(LECT2)-associated amyloidosis is a frequent cause of hepatic amyloidosis in the United States[J]. Blood, 2014, 123( 10): 1479- 1482. DOI: 10.1182/blood-2013-07-517938.
[15]	PALLADINI G, MERLINI G. What is new in diagnosis and management of light chain amyloidosis?[J]. Blood, 2016, 128( 2): 159- 168. DOI: 10.1182/blood-2016-01-629790.
[16]	CHOI M, PARK S, YI JK, et al. Overexpression of hepatic serum amyloid A1 in mice increases IL-17-producing innate immune cells and decreases bone density[J]. J Biol Chem, 2021, 296: 100595. DOI: 10.1016/j.jbc.2021.100595.
[17]	ROKITA H, SHIRAHAMA T, COHEN AS, et al. Differential expression of the amyloid SAA 3 gene in liver and peritoneal macrophages of mice undergoing dissimilar inflammatory episodes[J]. J Immunol, 1987, 139( 11): 3849- 3853.
[18]	LIN X, WATANABE K, KURAGANO M, et al. Aggregation of mouse serum amyloid a protein was promoted by amyloid-enhancing factors with the more genetically homologous serum amyloid A[J]. Int J Mol Sci, 2021, 22( 3): 1036. DOI: 10.3390/ijms22031036.
[19]	REZK T, GILBERTSON JA, ROWCZENIO D, et al. Diagnosis, pathogenesis and outcome in leucocyte chemotactic factor 2(ALECT2) amyloidosis[J]. Nephrol Dial Transplant, 2018, 33( 2): 241- 247. DOI: 10.1093/ndt/gfw375.
[20]	JERAJ N, HEGELE RA, BERBERICH AJ. Apolipoprotein genetic variants and hereditary amyloidosis[J]. Curr Opin Lipidol, 2021, 32( 2): 132- 140. DOI: 10.1097/MOL.0000000000000736.
[21]	UEDA M. Transthyretin: Its function and amyloid formation[J]. Neurochem Int, 2022, 155: 105313. DOI: 10.1016/j.neuint.2022.105313.
[22]	DAVOUDI Z, BIDARI F, JAMALI E, et al. Severe obstructive cholestasis and hypercalcemia caused by light-chain amyloidosis: a case report[J]. Iran J Med Sci, 2022, 47( 1): 73- 77. DOI: 10.30476/ijms.2021.88694.1942.
[23]	IWAI M, ISHII Y, MORI T, et al. Cholestatic jaundice in two patients with primary amyloidosis: ultrastructural findings of the liver[J]. J Clin Gastroenterol, 1999, 28( 2): 162- 166. DOI: 10.1097/00004836-199903000-00017.
[24]	BRICEÑO HC, GALVÁN C, SEGARRA M, et al. Cholestatic jaundice and constitutional syndrome as early manifestations of primary systemic amyloidosis[J]. Gastroenterol Hepatol, 2003, 26( 7): 424- 426. DOI: 10.1016/s0210-5705(03)70385-9.
[25]	HOWIE AJ. The nomenclature committee of the international society of amyloidosis: back towards“green birefringence”[J]. Amyloid, 2019, 26( 2): 96. DOI: 10.1080/13506129.2019.1597342.
[26]	SASAKI M, NAKANUMA Y, TERADA T, et al. Amyloid deposition in intrahepatic large bile ducts and peribiliary glands in systemic amyloidosis[J]. Hepatology, 1990, 12( 4 Pt 1): 743- 746. DOI: 10.1002/hep.1840120420.
[27]	MONZAWA S, TSUKAMOTO T, OMATA K, et al. A case with primary amyloidosis of the liver and spleen: radiologic findings[J]. Eur J Radiol, 2002, 41( 3): 237- 241. DOI: 10.1016/s0720-048x(01)00407-7.
[28]	SON RC, CHANG JC, CHOI JH. Primary hepatic amyloidosis: report of an unusual case presenting as a mass[J]. Korean J Radiol, 2011, 12( 3): 382- 385. DOI: 10.3348/kjr.2011.12.3.382.
[29]	KIM SH, HAN JK, LEE KH, et al. Abdominal amyloidosis: spectrum of radiological findings[J]. Clin Radiol, 2003, 58( 8): 610- 620. DOI: 10.1016/s0009-9260(03)00142-9.
[30]	NAIR AV, YADAV MK, UNNI MN, et al. Hepatic amyloidosis: something that can camouflage and deceive our perception![J]. Indian J Med Paediatr Oncol, 2017, 38( 2): 236- 239. DOI: 10.4103/ijmpo.ijmpo_46_16.
[31]	SYED U, CHING COMPANIONI RA, ALKHAWAM H, et al. Amyloidosis of the gastrointestinal tract and the liver: clinical context, diagnosis and management[J]. Eur J Gastroenterol Hepatol, 2016, 28( 10): 1109- 1121. DOI: 10.1097/MEG.0000000000000695.
[32]	TRIFANOV DS, DHYANI M, BLEDSOE JR, et al. Amyloidosis of the liver on shear wave elastography: case report and review of literature[J]. Abdom Imaging, 2015, 40( 8): 3078- 3083. DOI: 10.1007/s00261-015-0519-4.
[33]	LANZI A, GIANSTEFANI A, MIRARCHI MG, et al. Liver AL amyloidosis as a possible cause of high liver stiffness values[J]. Eur J Gastroenterol Hepatol, 2010, 22( 7): 895- 897. DOI: 10.1097/MEG.0b013e3283309d5b.
[34]	KARASUYAMA T, HONMA Y, KUMAMOTO K, et al. Hepatocyte growth factor and primary systemic amyloidosis[J]. J UOEH, 2021, 43( 2): 227- 233. DOI: 10.7888/juoeh.43.227.
[35]	YUAN ZY, ZHANG XX, WU YJ, et al. Serum amyloid A levels in patients with liver diseases[J]. World J Gastroenterol, 2019, 25( 43): 6440- 6450. DOI: 10.3748/wjg.v25.i43.6440.
[36]	ZHANG Y, ZHOU B, ZHANG F, et al. Amyloid-β induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway[J]. Diabetes, 2012, 61( 6): 1434- 1443. DOI: 10.2337/db11-0499.
[37]	MEAKIN PJ, MEZZAPESA A, BENABOU E, et al. The beta secretase BACE1 regulates the expression of insulin receptor in the liver[J]. Nat Commun, 2018, 9( 1): 1306. DOI: 10.1038/s41467-018-03755-2.
[38]	REZA MI, SYED AA, KUMARIYA S, et al. Pancreastatin induces islet amyloid peptide aggregation in the pancreas, liver, and skeletal muscle: An implication for type 2 diabetes[J]. Int J Biol Macromol, 2021, 182: 760- 771. DOI: 10.1016/j.ijbiomac.2021.04.064.
[39]	WESTERMARK GT, WESTERMARK P, NORDIN A, et al. Formation of amyloid in human pancreatic islets transplanted to the liver and spleen of nude mice[J]. Ups J Med Sci, 2003, 108( 3): 193- 203. DOI: 10.3109/2000-1967-113.
[40]	CIARALDI TP, GOLDBERG M, ODOM R, et al. In vitro effects of amylin on carbohydrate metabolism in liver cells[J]. Diabetes, 1992, 41( 8): 975- 981. DOI: 10.2337/diab.41.8.975.
[41]	SAGARE AP, DEANE R, ZLOKOVIC BV. Low-density lipoprotein receptor-related protein 1: a physiological Aβ homeostatic mechanism with multiple therapeutic opportunities[J]. Pharmacol Ther, 2012, 136( 1): 94- 105. DOI: 10.1016/j.pharmthera.2012.07.008.
[42]	CUI W, SUN Y, WANG Z, et al. Activation of liver X receptor decreases BACE1 expression and activity by reducing membrane cholesterol levels[J]. Neurochem Res, 2011, 36( 10): 1910- 1921. DOI: 10.1007/s11064-011-0513-3.
[43]	LIANG JS, SIPE JD. Recombinant human serum amyloid A(apoSAAp) binds cholesterol and modulates cholesterol flux[J]. J Lipid Res, 1995, 36( 1): 37- 46.
[44]	HONE E, MARTINS IJ, FONTE J, et al. Apolipoprotein E influences amyloid-beta clearance from the murine periphery[J]. J Alzheimers Dis, 2003, 5( 1): 1- 8. DOI: 10.3233/jad-2003-5101.
[45]	DEL GIUDICE R, IMBIMBO P, PIETROCOLA F, et al. Autophagy alteration in ApoA-I related systemic amyloidosis[J]. Int J Mol Sci, 2022, 23( 7): 3498. DOI: 10.3390/ijms23073498.
[46]	MUHAMMAD N, MURAKAMI T, INOSHIMA Y, et al. Long-term kinetics of AA amyloidosis and effects of inflammatory restimulation after disappearance of amyloid depositions in mice[J]. Clin Exp Immunol, 2015, 181( 1): 133- 141. DOI: 10.1111/cei.12615.
[47]	MIYAHARA H, DAI J, LI Y, et al. Macrophages in the reticuloendothelial system inhibit early induction stages of mouse apolipoprotein A-II amyloidosis[J]. Amyloid, 2022. DOI: 10.1080/13506129.2022.2153667.[ Online ahead of print]
[48]	JI YR, KIM HJ, BAE KB, et al. Hepatic serum amyloid A1 aggravates T cell-mediated hepatitis by inducing chemokines via Toll-like receptor 2 in mice[J]. J Biol Chem, 2015, 290( 20): 12804- 12811. DOI: 10.1074/jbc.M114.635763.
[49]	PILLING D, COX N, THOMSON MA, et al. Serum amyloid P and a dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin ligand inhibit high-fat diet-induced adipose tissue and liver inflammation and steatosis in mice[J]. Am J Pathol, 2019, 189( 12): 2400- 2413. DOI: 10.1016/j.ajpath.2019.08.005.
[50]	AN YA, CREWE C, ASTERHOLM IW, et al. Dysregulation of amyloid precursor protein impairs adipose tissue mitochondrial function and promotes obesity[J]. Nat Metab, 2019, 1( 12): 1243- 1257. DOI: 10.1038/s42255-019-0149-1.
[51]	JIANG B, WANG D, HU Y, et al. Serum amyloid A1 exacerbates hepatic steatosis via TLR4-mediated NF-κB signaling pathway[J]. Mol Metab, 2022, 59: 101462. DOI: 10.1016/j.molmet.2022.101462.
[52]	LI D, XIE P, ZHAO S, et al. Hepatocytes derived increased SAA1 promotes intrahepatic platelet aggregation and aggravates liver inflammation in NAFLD[J]. Biochem Biophys Res Commun, 2021, 555: 54- 60. DOI: 10.1016/j.bbrc.2021.02.124.
[53]	GARCIA J, CHANG R, STEINBERG RA, et al. Modulation of hepatic amyloid precursor protein and lipoprotein receptor-related protein 1 by chronic alcohol intake: Potential link between liver steatosis and amyloid-β[J]. Front Physiol, 2022, 13: 930402. DOI: 10.3389/fphys.2022.930402.
[54]	MURRAY KA, HUGHES MP, HU CJ, et al. Identifying amyloid-related diseases by mapping mutations in low-complexity protein domains to pathologies[J]. Nat Struct Mol Biol, 2022, 29( 6): 529- 536. DOI: 10.1038/s41594-022-00774-y.
[55]	LAVIE M, VOISSET C, VU-DAC N, et al. Serum amyloid A has antiviral activity against hepatitis C virus by inhibiting virus entry in a cell culture system[J]. Hepatology, 2006, 44( 6): 1626- 1634. DOI: 10.1002/hep.21406.
[56]	CAI Z, CAI L, JIANG J, et al. Human serum amyloid A protein inhibits hepatitis C virus entry into cells[J]. J Virol, 2007, 81( 11): 6128- 6133. DOI: 10.1128/JVI.02627-06.
[57]	YOU K, WANG Y, CHEN X, et al. Neutralizing serum amyloid a protects against sinusoidal endothelial cell damage and platelet aggregation during acetaminophen-induced liver injury[J]. Biochem Biophys Res Commun, 2023, 639: 20- 28. DOI: 10.1016/j.bbrc.2022.11.079.
[58]	TSUCHIYA H, SATO J, TSUDA H, et al. Serum amyloid A upsurge precedes standard biomarkers of hepatotoxicity in ritodrine-injected mice[J]. Toxicology, 2013, 305: 79- 88. DOI: 10.1016/j.tox.2013.01.012.
[59]	CONG M, ZHAO W, LIU T, et al. Protective effect of human serum amyloid P on CCl4-induced acute liver injury in mice[J]. Int J Mol Med, 2017, 40( 2): 454- 464. DOI: 10.3892/ijmm.2017.3028.
[60]	GETACHEW A, ABBAS N, YOU K, et al. SAA1/TLR2 axis directs chemotactic migration of hepatic stellate cells responding to injury[J]. iScience, 2021, 24( 5): 102483. DOI: 10.1016/j.isci.2021.102483.
[61]	BUNIATIAN GH, WEISKIRCHEN R, WEISS TS, et al. Antifibrotic effects of amyloid-beta and its loss in cirrhotic liver[J]. Cells, 2020, 9( 2): 452. DOI: 10.3390/cells9020452.
[62]	SASAKI M, YONEDA N, KITAMURA S, et al. A serum amyloid A-positive hepatocellular neoplasm arising in alcoholic cirrhosis: a previously unrecognized type of inflammatory hepatocellular tumor[J]. Mod Pathol, 2012, 25( 12): 1584- 1593. DOI: 10.1038/modpathol.2012.114.
[63]	CONNOLLY M, MARRELLI A, BLADES M, et al. Acute serum amyloid A induces migration, angiogenesis, and inflammation in synovial cells in vitro and in a human rheumatoid arthritis/SCID mouse chimera model[J]. J Immunol, 2010, 184( 11): 6427- 6437. DOI: 10.4049/jimmunol.0902941.
[64]	SEIDL SE, PESSOLANO LG Jr, BISHOP CA, et al. Toll-like receptor 2 activation and serum amyloid A regulate smooth muscle cell extracellular matrix[J]. PLoS One, 2017, 12( 3): e0171711. DOI: 10.1371/journal.pone.0171711.