【作者】 郭静；

【导师】 许荣焜；

【作者基本信息】 中国协和医科大学 ， 生理学， 2009， 硕士

【摘要】 本工作旨在探讨大豆提取物(soybean extract,简称SBE)对免疫低下小鼠免疫功能的影响以及从整体、细胞、分子水平研究SBE对裸鼠的人肝癌原位移植瘤的抑制作用,并探讨其细胞周期的调节机制,深层次揭示SBE的抗肿瘤作用,并为其临床应用提供科学依据。在第一部分中,采用在体实验,通过给小鼠腹腔注射环磷酰胺(Cyclophosphamide,CTX),建立免疫功能低下模型,观察SBE对免疫低下小鼠免疫功能的影响。结果表明,SBE能提高免疫低下小鼠的脾指数和血清IgG2a的水平,增加外周血的白细胞数、中性粒细胞和单核细胞百分率,增强NK细胞杀伤活性和腹腔巨噬细胞的吞噬功能,显著提高CTX造成的免疫低下小鼠的固有免疫和适应性免疫的作用,增强免疫功能。在第二部分中,建立裸鼠的人肝癌原位移植瘤的动物模型,研究SBE对肝癌的抑制作用,及其对肝癌细胞周期的调节机制。结果表明,SBE能够抑制裸鼠的人肝癌原位移植瘤的生长,提高荷瘤裸鼠的外周血白细胞数,增强免疫功能,降低血清AFP的水平,改善荷瘤裸鼠的肝功能;其部分机制可能是提高荷瘤裸鼠的免疫功能,同时,通过对p21、Cyclin D1/CDK4、CyclinE/CDK2、P-pRb蛋白表达的影响,引起肝癌细胞的G1期阻滞,抑制肿瘤细胞的增殖,从而抑制人肝癌裸鼠原位移植瘤的生长。更多还原

【Abstract】 The influence of soybean extract (SBE) on immune function of immunosuppressive micewas investigated in present study. The inhibitory effects of SBE on human orthotopictransplanted hepatocellular carcinoma (HCC) of nude mice and the mechanisms ofregulating the cell cycle were also investigated. In part I, immunosuppressive mice wasestablished by intraperitoneal injection of cyclophosphamide (CTX) to investigate theeffect of SBE on immune function of immunosuppressive mice. The data indicated thatspleen index and IgG2a level were significantly increased. The peripheral leucocytecount and the percentage of mononuclear leucocytes and neutrophils were markedlyraised. The activity of NK cell and peritoneal macrophage was remarkably stimulated.SBE significantly increased the immune function of CTX-induced immunosuppressivemice. Since SBE was shown to increase the immune function of CTX-inducedimmunosuppressive mice, we examined whether SBE would inhibt the growth of HCC.In part II, to combine our previous findings of HCC, the experimental model of humanorthotopic transplanted HCC of nude mice in vivo was used to investigated inhibitoryeffects of SBE on bearing cancer nude mice. We focused mainly on the cell cyclechanges of hepatocellular carcinoma cell. It was found that the growth of humanorthotopic transplanted HCC was inhibited by SBE. The peripheral leucocyte count ofnude mice was increased and AFP level of blood serum was decreased. Hepatic functionof bearing cancer nude mice was ameliorated by SBE. The hepatocellular carcinoma cellcount of G1 phase was significantly increased in SBE 30mg/kg group. The principalmechanism may relate with the changes in the expression of p21, Cyclin D1/CDK4,Cyclin E/CDK2 and P-pRb. The upregulation of p21 and downregulation of CyclinD1/CDK4, Cyclin E/CDK2 and P-pRb were related with G1 cell arrest and influencedthe G1/S transition.更多还原