【摘要】：本文評(píng)價(jià)氯喹與已上市抗HIV藥物聯(lián)合使用的體外抗HIV-1作用和抑制TLR7激動(dòng)劑引起的漿細(xì)胞樣樹(shù)突狀細(xì)胞(plasmacytoid dendritic cells,p DC)活化及Ⅰ型干擾素分泌上調(diào)的作用。采用MTT法檢測(cè)氯喹對(duì)C8166、TZM-bl、PBMC細(xì)胞的毒性。采用熒光素酶活性檢測(cè)方法、ELISA檢測(cè)p24抗原測(cè)定氯喹分別與雷特格韋(rategrivir,RAL)、恩夫韋肽(enfuvirtide,T-20)、茚地那韋(indinavir,IDV)和依法韋侖(efavirenz,EFV)聯(lián)合用藥抗HIV-1_(ⅢB)、HIV-1_(KM018)活性。流式細(xì)胞術(shù)檢測(cè)氯喹分別與RAL、IDV聯(lián)合使用對(duì)細(xì)胞p DC活化水平的影響。定量PCR檢測(cè)氯喹分別與RAL、IDV聯(lián)合使用對(duì)細(xì)胞內(nèi)IFN-α、IFN-βm RNA水平上調(diào)的影響。結(jié)果表明,氯喹對(duì)C8166、TZM-bl和PBMC細(xì)胞表現(xiàn)出較低的細(xì)胞毒性,半數(shù)細(xì)胞毒濃度(median cytotoxic concentration,CC_(50))分別為85.02±0.28、73.67±5.10和91.84±4.10μmol·L~(-1)。氯喹分別與RAL、T-20、IDV、EFV聯(lián)合用藥呈中度協(xié)同、強(qiáng)協(xié)同、相加、中度拮抗效果。氯喹分別與RAL、IDV的聯(lián)合使用相比于氯喹單藥使用對(duì)p DC活化水平和IFN-α、IFN-βm RNA表達(dá)水平的下調(diào)作用無(wú)統(tǒng)計(jì)學(xué)差異。本研究發(fā)現(xiàn)氯喹與不同類(lèi)型的已上市抗HIV藥物聯(lián)合使用呈現(xiàn)不同程度的協(xié)同、拮抗或相加抗HIV-1作用。氯喹分別與RAL、IDV聯(lián)合使用不影響氯喹對(duì)TLR7激動(dòng)劑引起的p DC活化和Ⅰ型干擾素分泌上調(diào)的抑制作用。本研究希望能夠給氯喹應(yīng)用于抗HIV治療提供參考,促進(jìn)氯喹更廣泛地應(yīng)用于臨床研究和治療中。
[Abstract]:The effects of chloroquine combined with anti-HIV drugs on anti-HIV-1 in vitro, inhibition of (plasmacytoid dendritic cells,p DC activation induced by TLR7 agonists and up-regulation of interferon I secretion in plasma-like dendritic cells were evaluated. MTT assay was used to detect the cytotoxicity of chloroquine to C8166, TZM and PBMCs. Determination of chloroquine with rategrivir,RAL, enfuvirtide,T-20, indinavir,IDV and efavirenz, by luciferase activity assay and ELISA detection of p24 antigen, respectively, were used to determine chloroquine and rethetrovir (rategrivir,RAL), nfwepeptide (enfuvirtide,T-20), indinavir (indinavir,IDV) and efavirenz, respectively. EFV combined with anti-HIV-1_ (鈪，

本文編號(hào)：2433747