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白藜芦醇联合治疗可减轻HIV蛋白酶抑制剂对大鼠体重的影响并增强心脏线粒体呼吸。

Resveratrol Co-Treatment Attenuates the Effects of HIV Protease Inhibitors on Rat Body Weight and Enhances Cardiac Mitochondrial Respiration.

作者信息

Symington Burger, Mapanga Rudo F, Norton Gavin R, Essop M Faadiel

机构信息

Cardio-Metabolic Research Group (CMRG), Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa.

Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

出版信息

PLoS One. 2017 Jan 20;12(1):e0170344. doi: 10.1371/journal.pone.0170344. eCollection 2017.

Abstract

Since the early 1990s human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) emerged as a global health pandemic, with sub-Saharan Africa the hardest hit. While the successful roll-out of antiretroviral (ARV) therapy provided significant relief to HIV-positive individuals, such treatment can also elicit damaging side-effects. Here especially HIV protease inhibitors (PIs) are implicated in the onset of cardio-metabolic complications such as type-2 diabetes and coronary heart disease. As there is a paucity of data regarding suitable co-treatments within this context, this preclinical study investigated whether resveratrol (RSV), aspirin (ASP) or vitamin C (VitC) co-treatment is able to blunt side-effects in a rat model of chronic PI exposure (Lopinavir/Ritonavir treatment for 4 months). Body weights and weight gain, blood metabolite levels (total cholesterol, HDL, LDL, triglycerides), echocardiography and cardiac mitochondrial respiration were assessed in PI-treated rats ± various co-treatments. Our data reveal that PI treatment significantly lowered body weight and cardiac respiratory function while no significant changes were found for heart function and blood metabolite levels. Moreover, all co-treatments ameliorated the PI-induced decrease in body weight after 4 months of PI treatment, while RSV co-treatment enhanced cardiac mitochondrial respiratory capacity in PI-treated rats. This pilot study therefore provides novel hypotheses regarding RSV co-treatment that should be further assessed in greater detail.

摘要

自20世纪90年代初以来,人类免疫缺陷病毒(HIV)/获得性免疫缺陷综合征(AIDS)成为全球健康大流行疾病,撒哈拉以南非洲地区受影响最为严重。虽然抗逆转录病毒(ARV)疗法的成功推广为HIV阳性个体带来了显著缓解,但这种治疗也可能引发有害的副作用。在此,尤其HIV蛋白酶抑制剂(PIs)与2型糖尿病和冠心病等心脏代谢并发症的发生有关。由于在这种情况下关于合适联合治疗的数据匮乏,这项临床前研究调查了白藜芦醇(RSV)、阿司匹林(ASP)或维生素C(VitC)联合治疗是否能够减轻慢性PI暴露大鼠模型(洛匹那韦/利托那韦治疗4个月)中的副作用。对接受PI治疗的大鼠±各种联合治疗进行体重和体重增加、血液代谢物水平(总胆固醇、高密度脂蛋白、低密度脂蛋白、甘油三酯)、超声心动图和心脏线粒体呼吸评估。我们的数据显示,PI治疗显著降低了体重和心脏呼吸功能,而心脏功能和血液代谢物水平未发现显著变化。此外,所有联合治疗均改善了PI治疗4个月后PI诱导的体重下降,而RSV联合治疗增强了PI治疗大鼠的心脏线粒体呼吸能力。因此,这项初步研究提供了关于RSV联合治疗的新假设,应进一步进行更详细的评估。

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