【摘要】 目的研究全反式维甲酸在视网膜母细胞瘤裸鼠移植瘤成瘤过程中的诱导分化作用及可能的机理。方法用腋部皮下注射SO-RB50细胞的方法对裸小鼠造模,定期观察肿瘤体积及重量、病理、电镜超微结构,增殖活性,检测各组肿瘤中CycinD1、CDK4、ICAM的表达水平。结果试验结束时给药组平均瘤重(2.750±0.302)g,于对照组的(7.150±1.228)g(P=0.008)及维甲酸缺乏组的(11.483±2.721)g(P=0.003)。镜检给药组肿瘤细胞大片出血坏死,对照组与原移植瘤的病理表现相同,维甲酸缺乏组核浆比大,核染色较对照组深。电镜示给药组细胞线粒体明显肿胀,空泡化,核糖体较对照组明显减少。对照组细胞同原移植瘤一致。维甲酸缺乏组游离核糖体较对照组多,溶酶体少见。给药组与对照组CyclinD1(P=0.012)、CDK4(P=0.010)差异有统计学意义,ICAM-1(P=0.071)未见有显著统计学差异;维甲酸缺乏组与对照组,CyclinD1(P=0.017)、CDK4(P=0.029)差异有统计学意义,ICAM-1(P=0.083)未见有显著统计学差异。结论维甲酸抑制视网膜母细胞瘤生长,维甲酸缺乏可促进视网膜母细胞瘤的生长,诱导分化作用的实现与调节CyclinD1和CDK4的表达水平有关。更多还原

【Abstract】 Objective To investigate the role and possible mechanism of all-trans retinoid acid in inducing differentiation of retinoblastoma in nude mice.Methods SO-RB50 suspense cell mixture was injected into bilateral armpits of male nude mice,and model of retinoblastoma nude mice was established.The size and weight of tumors were observed twice every week,tumors’ structure were recorded under microscope and electro-microscope,tumors’ DNA index was calculated,relative quantities of gene CyclinD1,CDK4 and ICAM-1 were measured by trans-transcription polymerase chain reaction and fluorescent quantity.Results At the end of the experiment,average tumor weight of ATRA group(2.750±0.302)g was lower than that of control group(7.150±1.228)g(P=0.008),and average tumor weight of Vitamin A deficient group(11.483±2.271)g(P=0.003).Under microscope,necrosis without inflammation was found in retinoblastoma cells in ATRA group,cells in control group appeared the same as those in original xenograft,retinoblastom cells in Vitamin A deficient group had a higher nuclear-plasma ratio than that of control group.Under electro-microscope,retinoblastoma cells in ATRA group contained swelled and bubble-like mitochondrion and much less ribosomes than those in control group.Cells in Vitamin A deficient group contained more free ribosomes and less lysosomes in the plasma than those in control group.Trans-transcription PCR and fluorescent quantity showed the relative quantity of CyclinD1 was the lowest in ATRA group(P=0.012) and highest in Vitamin A deficient group(P=0.017);the relative quantity of CDK4 was lowest in ATRA group(P=0.010) and highest in Vitamin A deficient group(P=0.029).There was no statistical significance in ICAM-1 between ATRA group and control group(P=0.071) or between Vitamin A deficient group and control group(P=0.083).Conclusion The growth of retinoblastoma xenograft in ATRA group was restrained by ATRA,and Vitamin A deficiency enhanced growth of retinoblastoma xenograft in nude mice.The effect of oral ATRA and Vitamin A deficiency in retinoblastoma xenograft in nude mice was related with the expression level of CyclinD1 and CDK4.更多还原