邻苯二甲酸酯对胆汁淤积性肝病影响的研究进展
DOI: 10.3969/j.issn.1001-5256.2023.01.035
利益冲突声明:所有作者均声明不存在利益冲突。
作者贡献声明:张佳怡负责查阅文章,撰写论文; 王建青负责修改文章并最后定稿。
-
摘要: 胆汁淤积性肝病是由于胆汁生成、排泄及代谢障碍,造成胆汁在肝脏沉积所致的一类常见肝胆疾病。目前胆汁淤积性肝病的致病因素尚未充分阐明,但有研究者认为环境因素可能在其中发挥重要作用。环境污染物邻苯二甲酸酯已被证实可干扰人类内分泌系统,对人体具有潜在毒性,危及肝肾功能,且可能增加肝内胆汁淤积的发生风险。基于此,本研究对邻苯二甲酸酯与胆汁淤积性肝病的关系进行综述,分别从临床研究、动物实验研究和体外实验研究及潜在机制进行总结,为胆汁淤积性肝病的预防以及临床治疗提供思路和参考。Abstract: Cholestatic liver disease is a common hepatobiliary disease caused by bile deposition in the liver due to the disorders of bile production, excretion, and metabolism. At present, the pathogenic factors for cholestatic liver disease have not been fully elucidated, but some researchers believe that environmental factors may play an important role in it. As environmental pollutants, phthalic acid esters (PAE) have been confirmed to interfere with human endocrine system, exert a potential toxic effect on the human body, endanger liver and kidney function, and increase the risk of intrahepatic cholestasis. On this basis, this article reviews the association between PAE and cholestatic liver disease and summarizes related clinical studies, animal experimental studies, in vitro experimental studies, and potential mechanisms, so as to provide ideas and references for the prevention and clinical treatment of cholestatic liver disease.
-
Key words:
- Cholestasis /
- Cholic Acid /
- Phthalic Acid Esters
-
[1] AN Z, BRASETH AL, SAHAR N. Acute cholangitis: Causes, diagnosis, and management[J]. Gastroenterol Clin North Am, 2021, 50(2): 403-414. DOI: 10.1016/j.gtc.2021.02.005. [2] CAO XX, GAO YQ, ZHANG WH, et al. Prevalence of cholestasis in inpatients with chronic liver disease in Shanghai[J]. Chin J Hepatol, 2015, 23(8): 569-573. DOI: 10.3760/cma.j.issn.1007-3418.2015.08.003.曹旬旬, 高月求, 张文宏, 等. 基于上海市住院慢性肝病患者胆汁淤积患病率的调查研究[J]. 中华肝脏病杂志, 2015, 23(8): 569-573. DOI: 10.3760/cma.j.issn.1007-3418.2015.08.003. [3] REICH M, SPOMER L, KLINDT C, et al. Downregulation of TGR5 (GPBAR1) in biliary epithelial cells contributes to the pathogenesis of sclerosing cholangitis[J]. J Hepatol, 2021, 75(3): 634-646. DOI: 10.1016/j.jhep.2021.03.029. [4] SCHATTENBERG JM, PARES A, KOWDLEY KV, et al. A randomized placebo-controlled trial of elafibranor in patients with primary biliary cholangitis and incomplete response to UDCA[J]. J Hepatol, 2021, 74(6): 1344-1354. DOI: 10.1016/j.jhep.2021.01.013. [5] LI H, GUAN Y, HAN C, et al. The pathogenesis, models and therapeutic advances of primary biliary cholangitis[J]. Biomed Pharmacother, 2021, 140: 111754. DOI: 10.1016/j.biopha.2021.111754. [6] PANAGIOTOU EM, OJASALO V, DAMDIMOPOULOU P. Phthalates, ovarian function and fertility in adulthood[J]. Best Pract Res Clin Endocrinol Metab, 2021, 35(5): 101552. DOI: 10.1016/j.beem.2021.101552. [7] MAO G, LIU H, DING Y, et al. Evaluation of combined developmental neurological toxicity of di (n-butyl) phthalates and lead using immature mice[J]. Environ Sci Pollut Res Int, 2020, 27(9): 9318-9326. DOI: 10.1007/s11356-019-06692-9. [8] FRANCESCHINI T, VASURI F, MURATORI P, et al. A practical histological approach to the diagnosis of autoimmune hepatitis: experience of an Italian tertiary referral center[J]. Virchows Arch, 2021, 479(5): 937-945. DOI: 10.1007/s00428-021-03122-5. [9] KETEMA RM, AIT BAMAI Y, MIYASHITA C, et al. Phthalates mixture on allergies and oxidative stress biomarkers among children: The Hokkaido study[J]. Environ Int, 2022, 160: 107083. DOI: 10.1016/j.envint.2022.107083. [10] van der MEER TP, CHUNG MK, van FAASSEN M, et al. Temporal exposure and consistency of endocrine disrupting chemicals in a longitudinal study of individuals with impaired fasting glucose[J]. Environ Res, 2021, 197: 110901. DOI: 10.1016/j.envres.2021.110901. [11] ROBINSON L, MILLER R. The impact of bisphenol A and phthalates on allergy, asthma, and immune function: a review of latest findings[J]. Curr Environ Health Rep, 2015, 2(4): 379-387. DOI: 10.1007/s40572-015-0066-8. [12] ANDJELKOVIĆ T, BOGDANOVIĆ D, KOSTIĆ I, et al. Phthalates leaching from plastic food and pharmaceutical contact materials by FTIR and GC-MS[J]. Environ Sci Pollut Res Int, 2021, 28(24): 31380-31390. DOI: 10.1007/s11356-021-12724-0. [13] HUANG YC, HUANG PR, LO YC, et al. Food processing and phthalate exposure: The nutrition and health survey in Taiwan (1993-1996 and 2005-2008)[J]. Front Nutr, 2021, 8: 766992. DOI: 10.3389/fnut.2021.766992. [14] GKRILLAS A, DIRVEN H, PAPADOPOULOU E, et al. Exposure estimates of phthalates and DINCH from foods and personal care products in comparison with biomonitoring data in 24-hour urine from the Norwegian EuroMix biomonitoring study[J]. Environ Int, 2021, 155: 106598. DOI: 10.1016/j.envint.2021.106598. [15] YAN Y, ZHU F, ZHU C, et al. Dibutyl phthalate release from polyvinyl chloride microplastics: Influence of plastic properties and environmental factors[J]. Water Res, 2021, 204: 117597. DOI: 10.1016/j.watres.2021.117597. [16] LOU ZQ, YU QF, SHEN XZ, et al. Effect of DEHP exposure in pregnant mice on neurobehavior of offsprings and its mechanism[J]. J Jilin Univ(Med Edit), 2021, 47(2): 323-329. DOI: 10.13481/j.1671-587X.20210210.楼张琪, 余起帆, 申雪知, 等. 孕鼠DEHP暴露对子代神经行为的影响及其机制[J]. 吉林大学学报(医学版), 2021, 47(2): 323-329. DOI: 10.13481/j.1671-587X.20210210. [17] CONLEY JM, LAMBRIGHT CS, EVANS N, et al. A mixture of 15 phthalates and pesticides below individual chemical no observed adverse effect levels (NOAELs) produces reproductive tract malformations in the male rat[J]. Environ Int, 2021, 156: 106615. DOI: 10.1016/j.envint.2021.106615. [18] WANG Y, QIAN H. Phthalates and their impacts on human health[J]. Healthcare (Basel), 2021, 9(5). DOI: 10.3390/healthcare9050603. [19] CHANG WH, HERIANTO S, LEE CC, et al. The effects of phthalate ester exposure on human health: A review[J]. Sci Total Environ, 2021, 786: 147371. DOI: 10.1016/j.scitotenv.2021.147371. [20] PREECE AS, SHU H, KNUTZ M, et al. Indoor phthalate exposure and contributions to total intake among pregnant women in the SELMA study[J]. Indoor Air, 2021, 31(5): 1495-1508. DOI: 10.1111/ina.12813. [21] ZHANG Y, HUANG B, HE H, et al. Urinary phthalate metabolites among workers in plastic greenhouses in western China[J]. Environ Pollut, 2021, 289: 117939. DOI: 10.1016/j.envpol.2021.117939. [22] ZHU YD. Effects of phthalate exposure during pregnancy on mental development and neuroinflammatory mechanism of preschool children[D]. Hefei: Anhui medical university, 2020.朱元多. 孕期邻苯二甲酸酯暴露对学龄前儿童智力发育的影响及神经炎性机制研究[D]. 合肥: 安徽医科大学, 2020. [23] WISE LA, AHERN TP, BROE A, et al. Periconceptional use of phthalate-containing medications and secondary sex ratio[J]. Environ Health Perspect, 2021, 129(9): 97701. DOI: 10.1289/EHP9494. [24] BAGEL S, DESSAIGNE B, BOURDEAUX D, et al. Influence of lipid type on bis (2-ethylhexyl)phthalate (DEHP) leaching from infusion line sets in parenteral nutrition[J]. JPEN J Parenter Enteral Nutr, 2011, 35(6): 770-775. DOI: 10.1177/0148607111414021. [25] LENG J, LI H, NIU Y, et al. Low-dose mono(2-ethylhexyl) phthalate promotes ovarian cancer development through PPARα-dependent PI3K/Akt/NF-κB pathway[J]. Sci Total Environ, 2021, 790: 147990. DOI: 10.1016/j.scitotenv.2021.147990. [26] SHNEIDER B, CRONIN J, VAN MARTER L, et al. A prospective analysis of cholestasis in infants supported with extracorporeal membrane oxygenation[J]. J Pediatr Gastroenterol Nutr, 1991, 13(3): 285-289. DOI: 10.1097/00005176-199110000-00008. [27] WANG JQ, GAO H, SHENG J, et al. Urinary concentrations of phthalate metabolites during gestation and intrahepatic cholestasis of pregnancy: a population-based birth cohort study[J]. Environ Sci Pollut Res Int, 2020, 27(11): 11714-11723. DOI: 10.1007/s11356-020-07675-x. [28] YANG Y, ZHANG J. Bile acid metabolism and circadian rhythms[J]. Am J Physiol Gastrointest Liver Physiol, 2020, 319(5): G549-G563. DOI: 10.1152/ajpgi.00152.2020. [29] IRUZUBIETA P, GOIKOETXEA-USANDIZAGA N, BARBIER-TORRES L, et al. Boosting mitochondria activity by silencing MCJ overcomes cholestasis-induced liver injury[J]. JHEP Rep, 2021, 3(3): 100276. DOI: 10.1016/j.jhepr.2021.100276. [30] MURTHA-LEMEKHOVA A, FUCHS J, GHAMARNEJAD O, et al. Influence of cytokines, circulating markers and growth factors on liver regeneration and post-hepatectomy liver failure: a systematic review and meta-analysis[J]. Sci Rep, 2021, 11(1): 13739. DOI: 10.1038/s41598-021-92888-4. [31] TAKESHITA A, IGARASHI-MIGITAKA J, NISHIYAMA K, et al. Acetyl tributyl citrate, the most widely used phthalate substitute plasticizer, induces cytochrome p450 3a through steroid and xenobiotic receptor[J]. Toxicol Sci, 2011, 123(2): 460-470. DOI: 10.1093/toxsci/kfr178. [32] DIAZ DE CERIO O, BILBAO E, IZAGIRRE U, et al. Toxicology tailored low density oligonucleotide microarray for the thicklip grey mullets (Chelon labrosus): Biomarker gene transcription profile after caging in a polluted harbour[J]. Mar Environ Res, 2018, 140: 265-277. DOI: 10.1016/j.marenvres.2018.06.009. [33] WOODS CG, BURNS AM, MAKI A, et al. Sustained formation of alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone radical adducts in mouse liver by peroxisome proliferators is dependent upon peroxisome proliferator-activated receptor-alpha, but not NADPH oxidase[J]. Free Radic Biol Med, 2007, 42(3): 335-342. DOI: 10.1016/j.freeradbiomed.2006.10.053. [34] BUCKNER SL, PRUITT AN, THOMAS CN, et al. Di-N-octylphthalate acts as a proliferative agent in murine cell hepatocytes by regulating the levels of TGF-β and pro-apoptotic proteins[J]. Food Chem Toxicol, 2018, 111: 166-175. DOI: 10.1016/j.fct.2017.11.005. [35] GAITANTZI H, HAKENBERG P, THEOBALD J, et al. Di (2-Ethylhexyl) phthalate and its role in developing cholestasis: An in vitro study on different liver cell types[J]. J Pediatr Gastroenterol Nutr, 2018, 66(2): e28-e35. DOI: 10.1097/MPG.0000000000001813. [36] GIJBELS E, VINKEN M. Mechanisms of drug-induced cholestasis[J]. Methods Mol Biol, 2019, 1981: 1-14. DOI: 10.1007/978-1-4939-9420-5_1. -