【摘要】：目的:將多囊脂質(zhì)體(MVLs)用于包載齊墩果酸(OA),制備一種新型給藥系統(tǒng)齊墩果酸多囊脂質(zhì)體(OA-MVLs),克服OA的難溶性缺點(diǎn),延長(zhǎng)藥物的消除時(shí)間,并初步驗(yàn)證OA-MVLs對(duì)正常人肝細(xì)胞L-02、人肝癌細(xì)胞HepG2和SMMC-7721細(xì)胞的抑制作用;擬考察利用最佳處方制備的OA-MVLs能否抑制肝癌細(xì)胞的遷移、侵襲,能否抑制腫瘤增長(zhǎng),降低毒副作用。方法:本研究采用已獲得的最優(yōu)處方制備OA-MVLs后,以肝癌細(xì)胞SMMC-7721和HepG2為細(xì)胞模型,分別給予不同劑量的OA-MVLs和OA,對(duì)細(xì)胞的活力、黏附、遷移和侵襲能力進(jìn)行評(píng)價(jià)。隨后,通過大鼠體內(nèi)毒性實(shí)驗(yàn)對(duì)OA-MVLs的毒副作用進(jìn)行考察。最后,構(gòu)建H22荷瘤小鼠模型,對(duì)OA-MVLs的抗腫瘤活性進(jìn)行檢測(cè)。結(jié)果:實(shí)驗(yàn)結(jié)果表明,OA-MVLs能顯著降低體外肝癌細(xì)胞的活力、黏附、遷移和侵襲。此外,當(dāng)濃度為160μmol/L時(shí)OA-MVLs對(duì)肝癌細(xì)胞有抑制作用,但是對(duì)正常肝細(xì)胞卻無影響。體內(nèi)毒性實(shí)驗(yàn)表明,低、中劑量的OA-MVLs對(duì)實(shí)驗(yàn)大鼠無毒副作用。OA-MVLs能抑制H22荷瘤小鼠腫瘤的生長(zhǎng)并且延長(zhǎng)其生存時(shí)間。結(jié)論:OA-MVLs能抑制體外肝癌細(xì)胞的生長(zhǎng)、黏附、遷移和侵襲,具有抗腫瘤活性,能抑制腫瘤的生長(zhǎng),低、中劑量的OA-MVLs更適用于肝癌治療的劑量選擇。
[Abstract]:Objective: to prepare a new delivery system of oleanolic acid polythylated liposome (OA-MVLs) by using polythylated liposome (MVLs) for encapsulating oleanolic acid (OA),. The inhibitory effects of OA-MVLs on normal human hepatocytes L-02, HepG2 and SMMC-7721 cells were preliminarily tested, and whether the OA-MVLs prepared with the best prescription could inhibit the migration, invasion, tumor growth and toxicity of hepatoma cells. Methods: in this study, OA-MVLs was prepared with the best prescription. The cell models of SMMC-7721 and HepG2 were used to evaluate the viability, adhesion, migration and invasion of hepatoma cells by different doses of OA-MVLs and OA, respectively. Then, the toxicity and side effects of OA-MVLs were investigated in vivo. Finally, the anti-tumor activity of OA-MVLs was detected by constructing H 22 tumor-bearing mice model. Results: the results showed that OA-MVLs could significantly reduce the viability, adhesion, migration and invasion of hepatoma cells in vitro. In addition, at the concentration of 160 渭 mol/L, OA-MVLs inhibited hepatoma cells, but had no effect on normal hepatocytes. In vivo toxicity test showed that low and middle dose of OA-MVLs had no side effects on experimental rats. OA-MVLs could inhibit tumor growth and prolong survival time of H22 tumor-bearing mice. Conclusion: OA-MVLs can inhibit the growth, adhesion, migration and invasion of hepatoma cells in vitro. It has anti-tumor activity and can inhibit tumor growth. Low dose OA-MVLs is more suitable for the treatment of liver cancer.
【學(xué)位授予單位】：西南醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R735.7

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