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匹伐他汀联合用药体外抗HIV-1活性研究*(PDF)

《云南中医学院学报》[ISSN:1000-2723/CN:53-1048/R]

期数:
2021年06期
页码:
15-20
栏目:
实验研究
出版日期:
2022-09-10

文章信息/Info

Title:
The Combined Anti-HIV-1 Effects of Pitavastatin and Antiviral Drugs in vitro
文章编号:
1000 - 2723(2021)06- 0015 - 06
作者:
杨金轩1罗荣华2陈欢1郑永唐2△
(1. 云南中医药大学中药学院,云南 昆明 650500;2. 中国科学院昆明动物研究所,中国科学院动物模型与人类疾病机理重点实验室,云南 昆明 650223)
Author(s):
YANG Jinxuan1 LUO Ronghua2 CHEN Huan1 ZHENG Yongtang2
(1. College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China; 2. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China)
关键词:
他汀匹伐他汀抗HIV-1活性联合用药
Keywords:
statins pivastatin anti-HIV-1 activity drug combination
分类号:
R965.1
DOI:
10.19288/j.cnki.issn.1000-2723.2021.06.003
文献标识码:
A
摘要:
目的 研究他汀类药物体外抗人类免疫缺陷病毒I型(human immunodeficiency virus type 1,HIV-1)活性并评价匹伐他汀与其它抗HIV药物联合使用时的抗病毒活性。方法 采用噻唑蓝(MTT)比色法测定他汀类药物对C8166细胞的毒性作用;合胞体计数检测他汀类药物对实验株HIV-1IIIB诱导C8166细胞病变的抑制作用;酶联免疫吸附测定法(ELISA)测定HIV-1 p24抗原检测他汀类药物对实验株HIV-1IIIB急性感染C8166细胞中病毒复制的抑制作用以及匹伐他汀与其它抗HIV药物联合用药的联合效应。结果 他汀类药物中匹伐他汀具有显著体外抗HIV-1活性,匹伐他汀与核苷类逆转录酶抑制剂(替诺福韦、恩曲他滨、拉米夫定、齐多夫定)和蛋白酶抑制剂(茚地那韦和达芦那韦)联合用药时,药物间呈现协同作用;与非核苷类逆转录酶抑制剂(依曲韦林)联合用药时,药物间呈现拮抗作用;与整合酶链转移抑制剂(雷特格韦和度鲁特韦)联合用药时,药物间呈现相加作用。结论 匹伐他汀除与依曲韦林联合时药物间呈现拮抗作用外,与其它抗HIV药物联用均呈现相加或协同作用。
Abstract:
Objective To investigate the in vitro anti-HIV-1 activity of statins and to evaluate the antiviral of pitavastatin in combination with other anti-HIV drugs. Methods The cytotoxicity of statins on C8166 cells was determined using the MTT assay. The inhibitory effect of statins on HIV-1IIIB-induced cytopathic effect was measured by counting the number of syncytia. The inhibitory effect of statins on the viral replication in C8166 cells acutely infected with laboratory-adapted strains HIV-1IIIB was detected by ELISA. The combination of pitavastatin and anti-HIV drugs with the different targets was measured by ELISA. Results Among statins, pivastatin has significant anti-HIV-1 activity in vitro. The combination of pivastatin with nucleoside reverse transcriptase inhibitors(tenofovir, emtricitabine, lamivudine and zidovudine) and protease inhibitors(indinavir and darunavir) showed synergistic effect. The combination of pivastatin with non-nucleoside reverse transcriptase inhibitor(etravirine) showed antagonism effect. The combination of pivastatin with integrase strand transfer inhibitors(raltegravir and dolutegravir) showed additive effect. Conclusion Pitavastatin showed synergistic or additive effects when combined with other anti-HIV drugs, except for antagonism when combined with etravirine.

参考文献/References

[1] 李涛. 他汀类药物临床多效性研究进展[J]. 临床合理用药杂志,2021,14(23):179-181.
[2] CHEN L W,LIN C S,TSAI M C,et al. Pitavastatin exerts potent anti-inflammatory and immunomodulatory effects via the suppression of AP-1 signal transduction in human T cells[J]. Int J Mol Sci,2019,20(14):3534.
[3] BAEKKEN M,OS I,SANDVIK L,et al. Hypertension in an urban HIV-positive population compared with the general population:influence of combination antiretroviral therapy[J]. J Hypertens,2008,26(11):2126-2133.
[4] ECKARD A R,MEISSNER E G,SINGH I,et al. Cardiovascular disease,statins,and HIV[J]. J Infect Dis,2016, 214 Suppl 2(Suppl 2):S83-S92.
[5] 王凌航,赵红心,毛羽. 艾滋病高效抗反转录病毒治疗并发高脂血症的研究进展[J]. 中国艾滋病性病,2010,16(3):319-322.
[6] DAD STUDY GROUP,FRIIS-M?覫LLER N,REISS P,et al. Class of antiretroviral drugs and the risk of myocardial infarction[J]. N Engl J Med,2007,356(17):1723-1735.
[7] RETHY L,FEINSTEIN M J,SINHA A,et al. Coronary microvascular dysfunction in HIV:a review[J]. J Am Heart Assoc,2020,9(1):e014018.
[8] BOCCARA F,LANG S,MEULEMAN C,et al. HIV and coronary heart disease:time for a better understanding[J]. J Am Coll Cardiol,2013,61(5):511-523.
[9] CHELVANAMBI S,GUPTA S K,CHEN X,et al. HIV-Nef protein transfer to endothelial cells requires Rac1 activation and leads to endothelial dysfunction implications for statin treatment in HIV patients[J]. Circ Res, 2019, 125(9):805-820.
[10] LIU B F,ZHANG X,ZHANG W Y,et al. Lovastatin inhibits HIV-1-induced MHC-I downregulation by targeting Nef-AP-1 complex formation:a new strategy to boost immune eradication of HIV-1 infected cells[J]. Front Immunol,2019,10:2151.
[11] PRIYA DHARSHINI K,FANG H,RAMYA DEVI D,et al. pH-sensitive chitosan nanoparticles loaded with dolutegravir as milk and food admixture for paediatric anti-HIV therapy[J]. Carbohydr Polym,2021,256:117440.
[12] CHEN H,ZHANG R,LUO R H,et al. Anti-HIV activities and mechanism of 12-O-tricosanoylphorbol-20-acetate,a novel phorbol ester from Ostodes katharinae[J]. Molecules,2017,22(9):1498.
[13] LIU G J,WANG J P,XIAO J C,et al. Preparation and characterization of three monoclonal antibodies against HIV-1 p24 capsid protein[J]. Cell Mol Immunol,2007,4(3):203-208.
[14] WANG R R,YANG Q H,LUO R H,et al. Azvudine,a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro [J]. PLoS One,2014,9(8):e105617.
[15] 郑玉贵. CCR5拮抗剂DC521042和DC521043体外抗HIV-1药效学研究[D]. 昆明:昆明医科大学,2019.
[16] CHOU T C. Theoretical basis,experimental design,and computerized simulation of synergism and antagonism in drug combination studies[J]. Pharmacol Rev, 2006, 58(3):621-681.
[17] 王士群,朱宇珍,郑学宝. Chou-Talalay在抗肿瘤联合用药中的研究应用概况[J]. 中国现代应用药学,2013,30(4):449-453.
[18] JILEK B L,ZARR M,SAMPAH M E,et al. A quantitative basis for antiretroviral therapy for HIV-1 infection[J]. Nat Med,2012,18(3):446-451.
[19] HUANG X S,LUO R H,HU X L,et al. The new NNRTI ACC007 combined with lamivudine and tenofovir disoproxil fumarate show synergy anti-HIV activity in vitro[J]. Curr HIV Res,2020,18(5):332-341.
[20] ROSENSON R S,COLANTONIO L D,BURKHOLDER G A,et al. Trends in utilization of statin therapy and contraindicated statin use in HIV-infected adults treated with antiretroviral therapy from 2007 through 2015[J]. J Am Heart Assoc,2018,7(24):e010345.
[21] BOCCARA F,KUMAR P N,CARAMELLI B,et al. Evolocumab in HIV-infected patients with dyslipidemia:primary results of the randomized,double-blind BEIJERINCK study[J]. J Am Coll Cardiol,2020,75(20):2570-2584.
[22] SMYTH L,BLUNT D N,GATOV E,et al. Statin and cyclooxygenase-2 inhibitors improve survival in newly diagnosed diffuse large B-cell lymphoma: a large population-based study of 4913 subjects[J]. Br J Haematol,2020,191(3):396-404.
[23] REN Q W,YU S Y,TENG T K,et al. Statin associated lower cancer risk and related mortality in patients with heart failure[J]. Eur Heart J,2021,42(32):3049-3059.
[24] ZISSIMOPOULOS J M,BARTHOLD D,BRINTON R D,et al. Sex and race differences in the association between statin use and the incidence of alzheimer disease[J]. JAMA Neurol,2017,74(2):225-232.
[25] ELAHI S,WEISS R H,MERANI S. Atorvastatin restricts HIV replication in CD4+ T cells by upregulation of p21[J]. AIDS,2016,30(2):171-183.
[26] NAMASIVAYAM V,VANANGAMUDI M,KRAMER V G,et al. The journey of HIV-1 non-nucleoside reverse transcriptase inhibitors(NNRTIs)from lab to clinic[J]. J Med Chem,2019,62(10):4851-4883.

备注/Memo

备注/Memo:
收稿日期: 2021 - 12- 06
* 基金项目: 国家自然科学基金(82060670);云南省重大科技专项计划(202103AC100005)
第一作者简介: 杨金轩(1995-),女,在读硕士研究生,研究方向:抗HIV药物药理药效。
△通信作者: 郑永唐,E-mail:zhengyt@mail.kiz.ac.cn
更新日期/Last Update: 1900-01-01