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新内毒素诱导的胆汁盐输出泵抗体产生与肝切除术后细菌感染有关。

De Novo Endotoxin-Induced Production of Antibodies against the Bile Salt Export Pump Associated with Bacterial Infection following Major Hepatectomy.

机构信息

Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.

出版信息

Biomed Res Int. 2018 Apr 23;2018:6197152. doi: 10.1155/2018/6197152. eCollection 2018.

DOI:10.1155/2018/6197152
PMID:29850541
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5937615/
Abstract

BACKGROUND

Clinically severe infection-related inflammation after major liver resection may cause hyperbilirubinemia. This study aims to clarify the impact of bacterial infection and endotoxins on the hepatobiliary transporter system and to explore possible mechanisms of endotoxin-related postoperative hyperbilirubinemia.

METHOD

Mice that underwent major hepatectomy with removal of at least 70% of liver volume were exposed to lipopolysaccharide (LPS) at different dosages. Subsequently, hepatobiliary transporter compounds related to bile salt excretion were further investigated.

RESULTS

The expression of genes related to hepatobiliary transporter compounds was not significantly different in the liver tissue of mice after major hepatectomy and LPS exposure. However, bile salt export pump (BSEP) protein expression within the liver tissue of mice treated with LPS after major hepatectomy was relatively weaker and was even further reduced in the high-dose LPS group. The formation of antibodies against the BSEP in response to endotoxin exposure was also detected.

CONCLUSION

This study illustrates a possible mechanism whereby the dysfunction of hepatobiliary transporter systems caused by endotoxin-induced autoantibodies may be involved in the development of postoperative jaundice associated with bacterial infection after major hepatectomy.

摘要

背景

肝叶切除术后严重的感染相关炎症可能导致高胆红素血症。本研究旨在阐明细菌感染和内毒素对肝胆转运系统的影响,并探讨内毒素相关术后高胆红素血症的可能机制。

方法

将至少 70%肝体积切除的肝叶切除术的小鼠暴露于不同剂量的脂多糖(LPS)。随后,进一步研究了与胆汁盐排泄相关的肝胆转运化合物。

结果

肝叶切除和 LPS 暴露后,小鼠肝组织中与肝胆转运化合物相关的基因表达无明显差异。然而,肝组织中 LPS 处理后的 BSEP 蛋白表达相对较弱,高剂量 LPS 组的表达进一步降低。还检测到针对内毒素暴露形成的 BSEP 抗体。

结论

本研究阐明了一种可能的机制,即内毒素诱导的自身抗体引起的肝胆转运系统功能障碍可能参与了肝叶切除术后细菌感染相关的术后黄疸的发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1867/5937615/19cd9045f124/BMRI2018-6197152.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1867/5937615/eda962c3ea8e/BMRI2018-6197152.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1867/5937615/c148e8b17f80/BMRI2018-6197152.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1867/5937615/5c77b9398302/BMRI2018-6197152.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1867/5937615/a1945442503c/BMRI2018-6197152.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1867/5937615/eb02e73e353c/BMRI2018-6197152.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1867/5937615/19cd9045f124/BMRI2018-6197152.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1867/5937615/eda962c3ea8e/BMRI2018-6197152.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1867/5937615/c148e8b17f80/BMRI2018-6197152.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1867/5937615/5c77b9398302/BMRI2018-6197152.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1867/5937615/a1945442503c/BMRI2018-6197152.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1867/5937615/eb02e73e353c/BMRI2018-6197152.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1867/5937615/19cd9045f124/BMRI2018-6197152.006.jpg

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本文引用的文献

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The Preference for Anterior Approach Major Hepatectomy: Experience Over 3 Decades and a Propensity Score-Matching Analysis in Right Hepatectomy for Hepatocellular Carcinoma.对肝切除前路入路的偏好:三十年经验及肝细胞癌右半肝切除的倾向评分匹配分析
Medicine (Baltimore). 2015 Aug;94(34):e1385. doi: 10.1097/MD.0000000000001385.
2
Quantified Risk Assessment for Major Hepatectomy via the Indocyanine Green Clearance Rate and Liver Volumetry Combined with Standard Liver Volume.通过吲哚菁绿清除率和肝脏容积测量结合标准肝脏体积对肝大部切除术进行量化风险评估。
J Gastrointest Surg. 2015 Jul;19(7):1305-14. doi: 10.1007/s11605-015-2846-8. Epub 2015 May 7.
3
Rituximab as therapy for the recurrence of bile salt export pump deficiency after liver transplantation.
利妥昔单抗治疗肝移植后胆汁盐输出泵缺陷复发。
Liver Transpl. 2013 Dec;19(12):1403-10. doi: 10.1002/lt.23754.
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Bile formation and secretion.胆汁的形成和分泌。
Compr Physiol. 2013 Jul;3(3):1035-78. doi: 10.1002/cphy.c120027.
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Systemic causes of cholestasis.胆汁淤积的系统性病因。
Clin Liver Dis. 2013 May;17(2):301-17. doi: 10.1016/j.cld.2012.11.001. Epub 2013 Jan 26.
6
A risk model to predict 90-day mortality among patients undergoing hepatic resection.用于预测肝切除术后 90 天死亡率的风险模型。
J Am Coll Surg. 2013 Jun;216(6):1049-56. doi: 10.1016/j.jamcollsurg.2013.01.004. Epub 2013 Mar 9.
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The bile salt export pump (BSEP) in health and disease.在健康和疾病中的胆汁盐输出泵(BSEP)。
Clin Res Hepatol Gastroenterol. 2012 Dec;36(6):536-53. doi: 10.1016/j.clinre.2012.06.006. Epub 2012 Jul 12.
8
Adverse outcomes in patients with postoperative ascites after liver resection for hepatocellular carcinoma.肝癌肝切除术后并发术后腹水患者的不良结局。
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Comprehensive proteomic analysis of human bile.人胆汁的综合蛋白质组学分析。
Proteomics. 2011 Dec;11(23):4443-53. doi: 10.1002/pmic.201100197. Epub 2011 Nov 4.
10
Hepatobiliary transporter expression and post-operative jaundice in patients undergoing partial hepatectomy.行肝部分切除术患者的肝胆转运体表达与术后黄疸。
Liver Int. 2012 Jan;32(1):119-27. doi: 10.1111/j.1478-3231.2011.02625.x. Epub 2011 Aug 25.