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抗逆转录病毒疗法对HIV患者肝脏肝细胞和内皮的不良影响:超微结构视角

Adverse effects of antiretroviral therapy on liver hepatocytes and endothelium in HIV patients: An ultrastructural perspective.

作者信息

Chwiki Sarah, Campos Maria Mercedes, McLaughlin Mary E, Kleiner David E, Kovacs Joseph A, Morse Caryn G, Abu-Asab Mones S

机构信息

a Section of Histopathology , National Eye Institute, NIH , Bethesda , MD , USA.

b Laboratory of Immunoregulation , National Institute of Allergy and Infectious Diseases, NIH , Bethesda , MD , USA.

出版信息

Ultrastruct Pathol. 2017 Mar-Apr;41(2):186-195. doi: 10.1080/01913123.2017.1282066. Epub 2017 Feb 28.

Abstract

Human immunodeficiency virus and antiretroviral therapy (ART) together can be far more detrimental to liver cells than either of the two unaided. However, ultrastructural aspects of the synergistic effects of HIV and ART have been understudied. In a patient cohort receiving ART, this study characterizes ultrastructurally sinusoidal degeneration, hepatocytic aberrations, mitochondrial dysfunction, accumulation of bulky lipid droplets (steatosis), and occlusion of sinusoidal lumina. Mitochondrial dysfunction causes the accumulation of acetyl-CoA which leads to insulin upregulation and resistance, lipid synthesis, and steatosis. Lipid droplets deposited in the sinusoids could be the source of the blood's lipid profile alterations in HIV patients on ART.

摘要

人类免疫缺陷病毒(HIV)与抗逆转录病毒疗法(ART)共同作用对肝细胞造成的损害可能远大于二者单独作用时的任何一方。然而,HIV与ART协同作用的超微结构方面一直未得到充分研究。在一个接受ART的患者队列中,本研究对超微结构特征进行了描述,包括肝血窦变性、肝细胞畸变、线粒体功能障碍、大量脂滴积聚(脂肪变性)以及肝血窦管腔阻塞。线粒体功能障碍导致乙酰辅酶A积累,进而引起胰岛素上调和抵抗、脂质合成以及脂肪变性。沉积在肝血窦中的脂滴可能是接受ART的HIV患者血液脂质谱改变的来源。

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