应用细胞模型初筛抗人免疫缺陷病毒药物

Screening of anti-HIV agents with cell models

目的探讨采用已建立的细胞模型初筛抗人免疫缺陷病毒(HIV)药物的可靠性。方法以齐多夫定为阳性对照,使用HIV-1急性感染系统(MT-4/HIV-1ⅢB)、HIV-1耐药性毒株系统(MT-4/3TC耐药株)、HIV-1慢性感染系统(H9/HIV-1ⅢB)和HIV-1临床分离株感染系统(PBMC/HIV-1GX02),分别测定药物的细胞毒性和抗HIV-1活性,计算药物的半数细胞毒性浓度(TC50)、半抑制浓度(IC50)和治疗指数(TI)。同时对4种药物DPC961、牛膝多糖、艾乃吉1号和痰热清注射液进行了抗HIV活性检测。结果测定了齐多夫定在4种细胞-病毒系统的TC50,IC50和TI与文献报道相近。DPC961在4种细胞/病毒培养系统的TI分别为979,5348,3912和2745;牛膝多糖分别为323,223,2777和173;艾乃吉1号仅在MT-4/HIV-1ⅢB模型上T1为2.6。结论使用本细胞模型通过检测药物的TC50,IC50及TI进行药物初筛是可靠的。药物DPC961、牛膝多糖和艾乃吉Ⅰ号具有不同程度的体外抗HIV-1活性,痰热清注射液未检测到抗HIV-1活性。

AIM To evaluate the reliability of 4 cell models established for anti-HIV agent screening in vitro. METHODS In HIV-1 acute infection system （MT-4/HIV-1ⅢB）,HIV-1 resistant strain system （MT-4/3TC-resistant strain）,HIV-1 chronical infection （H9/HIV-1ⅢB） and HIV-1 clinically isolated one （PBMC/HIV-1 GX02）,these agents＇ cytotoxicity and anti-HIV activity were determined respectively,and their TC50,IC50 and therapeutic indexes（TI） were calculated,and zidovudine was as the positive control of these experiments. Four agents such as DPC961,Achyranthes bidentata polysaccharides,Ainaiji Ⅰand Tanreqing injection were determined. RESULTS The TC50,IC50 and TI of zidovudine were determined on these 4 cell models,and were similar with the reported. TI of DPC961 on these models were 979,5348,3912,and 2745,respectively; TI of A. bidentata polysaccharides were 323,223,2777 and 173,respectively; TI of AinaijiⅠ on MT-4/ HIV-1 ⅢB model was 2.6. CONCLUSIONThe cell models used in this experiment to screen anti-HIV agents by determining the TC50,IC50 and TI are reliable. DPC961,A. bidentata polysaccharides and AinaijiⅠ show different levels of anti-HIV activities except Tanreqing injection in these cell models.