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青蒿素衍生物和某些天然化合物抗HIV-1活性的研究
文献类型：学位论文
| 作者 | 李劲光 |
| 学位类别 | 硕士 |
| 答辩日期 | 1998-09 |
| 授予单位 | 中国科学院研究生院 |
| 授予地点 | 北京 |
| 导师 | 贲昆龙 |
| 关键词 | 人免疫缺陷病毒（HIV） 抗HIV药物 猴逆转录D型病毒（SRV1） 青蒿素衍生物 天然化合物 中草药配方 MTT比色法 合胞体 间接免疫荧光法 p24半定量ELISA 协同作用 |
| 中文摘要 | 对生活在发展中国家的90%以上的HIV感染者而言，现有FDA已批准的抗HIV药物的价格十分昂贵。中国也是发展中国家，但HIV感染者已遍布全国，其数量正急剧增长，这必将对生产力和国民经济建设产生严重影响。为预防艾滋病蔓延，我们在进行宣传教育的同时，务必研制开发有我国特色的、高效的、便宜的抗HIV药物。因此，我们在抗猴逆转录D型病毒（SRV1）活性研究基础上，对SM458等24个青蒿素衍生物进行了抗HIV-1活性的深入研究。同时，为充分利用我国丰富的自然资源，我们还研究了20个天然化合物和中草药配方。除应用MTT比色法外，我们还采用了另外3种体外抗HIV-1活性研究的实验，如合胞体形成抑制，间接免疫荧光法（IFA），p24半定量ELISA等。此外，我们还研究了SM458、SM486和肝龙与AZT的协同作用，并进一步重复了SM458和SM486抗SRV1活性的研究。结果表明：AZT的抗SRV1/HIV-1活性十分显著，SM458和SM486 也有较高的抗SRV1活性，其选择指数均接近100；但除了SM458较稳定地表现微弱的抗HIV-1活性外，其它23个青蒿素衍生物没有活性；为初步探索SM458和SM486抗SRV1/HIV-1活性差异的机理，我们进行细胞融合阻断实验，结果表明其作用靶点并非融合。由此说明：SRV1虽然与HIV-1同属灵长类逆传录病毒，但以SRV1进行的抗病毒研究结果，不能完全与抗HIV-1的活性相符合，必须以直接用HIV-1所做的研究为依据。令人鼓舞的是，肝龙表现稳定的抗HIV-1活性，值得进一步深入研究。而其它19个样品中，仅桑黄素、桑白皮和GE-II表现很微弱的活性，JK028和V1-1-Na有待确证。SM458、SM486和肝龙与AZT无协同作用。 |
| 英文摘要 | Even though most pharmaceutical companies have cut the prices of their products in developing countries, all anti-HIV drugs currently approved by FDA are still too expensive to be used for more than 90% HIV-1-infected people living in those countries. In China, the number of people infected by HIV has been increasing intensively, which would severely damage the development of our society. To effectively control the spread of AIDS, we must prevent more infections by means of education. At the same time, we have to develop some highly effective and cheap drugs with Chinese characteristics. Based on our previous anti-SRV1 studies, we did further investigation on anti-HIV activities of 24 artemisinin derivatives. In addition, in order to make rational use of the abundant natural resources of our country, we investigated 20 other natural compounds or Chinese herb formula. Besides MTT colorimetric assay, we adopted 3 other tests, such as inhibition of syncytium formation, indirect immunofluorescence assay (IFA), semi-quantitative enzyme-linked immunosorbent assay (ELISA). Moreover, the combinational interaction between AZT and the other compounds was also tested. As the positive control, the anti-HIV-1/SRV1 activities of AZT were remarkably strong; and SM458 and SM486 showed good anti-SRV1 activities with their selective indices (SI) near 100. Unfortunately, except that SM458 demonstrated constantly feeble anti-HIV-1 activities, all 23 other artemisinin derivatives did not. Furthermore, we did the preliminary assay on the inhibition of cell fusion induced by HIV-1 and SRV1 in order to explore the mechanism on the differences between the anti-SRV1 and anti-HIV-1 activities of SM458 and SM486. The results showed that the target in antiviral activities for both compounds was not at the fusion. Therefore, the use of SRV1 as the anti-HIV-1 drug screening model virus should be careful, even though both HIV-1 and SRV1 belong to primate retroviruses. Encouragingly, Ganlong, a compound from insect, constantly showed anti-HIV-1 activities, and is worth to be investigated further. However, among 19 other samples, only morusin, sangbaipi and GE-II manifested feeble antiviral activities, those of V1-1-Na and JK028 needed to be further confirmed. SM458, SM486 and Ganlong did not display synergetic interaction with AZT in anti-HIV-1 activities. |
| 语种 | 中文 |
| 公开日期 | 2010-10-15 |
| 源URL | [http://159.226.149.42:8088/handle/152453/6205]  |
| 专题 | 昆明动物研究所_其他 |
| 推荐引用方式 GB/T 7714 | 李劲光. 青蒿素衍生物和某些天然化合物抗HIV-1活性的研究[D]. 北京. 中国科学院研究生院. 1998. |
入库方式： OAI收割
来源：昆明动物研究所
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