H-ras12V转基因小鼠肝癌进展过程中外周血淋巴细胞比例及活性的变化  

Changes of proportions of T and B lymphocytes and their activation in peripheral blood of H-ras12V transgenic hepatic tumor in mice

作　　者：聂鑫[1] 王康伟[1] 张敏[1] 王福金[1] 王爱国[1] 王靖宇[1] 

机构地区：[1]大连医科大学实验动物中心,辽宁大连116044

出　　处：《肿瘤》2016年第1期20-27,共8页Tumor

基　　金：国家自然科学基金资助项目(编号:30872950)~~

摘　　要：目的:检测H-ras12V转基因雄性小鼠肝肿瘤发生和发展过程中,其外周血中T、B淋巴细胞表型及活性T、B淋巴细胞所占比例的变化,以期探讨肝肿瘤与淋巴细胞之间相互作用的机制。方法:采用FCM法分别检测3、5和9月龄H-ras12V转基因雄性小鼠及正常健康C57BL/6J雄性小鼠(对照组)外周血中不同T、B淋巴细胞表型所占的比例和活性T、B淋巴细胞所占的比例,同时对所有小鼠的肝组织进行病理学诊断。结果:3月龄的H-ras12V转基因雄性小鼠和3、5和9月龄的对照组正常健康雄性小鼠的肝脏中均未出现显著的病理学改变。5月龄的H-ras12V转基因雄性小鼠的肝脏中出现多发性结节,而9月龄的H-ras12V转基因雄性小鼠的肝脏中则发生了多发性肝肿瘤。与同月龄的正常健康雄性小鼠相比J3、5和9月龄H-rasl2V转基因雄性小鼠外周血中B淋巴细胞(sIgM^+CD23^+和sIgM^+B220^+)所占比例均明显降低(P值均<0.01),5和9月龄H-ras12V转基因雄性小鼠中活性B淋巴细胞(CD19^+CD69^+)所占的比例也均发生明显降低(P值均<0.05),并且随着月龄的增加及H-ras12V转基因雄性小鼠肝肿瘤的发生和发展,外周血中B淋巴细胞和活性B淋巴细胞所占的比例呈逐渐降低的趋势。与同月龄正常健康雄性小鼠相比,3和5月龄H-ras12V转基因雄性小鼠的外周血中T淋巴细胞(CD3e^+)所占的比例及活性T淋巴细胞(CD3e^+CD69^+和CD3e^+CD25^+)所占的比例均无明显变化(P>0.05),但9月龄H-ras12V转基因雄性小鼠外周血中T淋巴细胞所占比例及活性T淋巴细胞所占比例均显著降低(P值均<0.05)。结论:随着H-ras12V转基因雄性小鼠肝肿瘤的恶化,其外周血中T、B淋巴细胞及活性T、B淋巴细胞所占的比例显著降低。Objective： To investigate the proportions of T and B lymphocytes as well as their activation in peripheral blood cells from H-ras12V transgenic male mice in different progression stages of hepatic tumor, and to explore the mechanism of interaction between hepatocellular carcinoma and lymphocytes. Methods： The proportions of T and B lymphocytes and their activation in peripheral white blood cells from normal healthy C57BL/6J （non-transgenic） and H-ras12V transgenic male mice at ages of 3, 5 and 9 months were detected by FCM. The pathologic changes of liver tissues in H-ras12Vtransgenic male mice at ages of 3, 5 and 9 months were also examined. Results： No obvious pathologic changes were detected in the liver tissues of H-ras12V transgenic male mice aged 3 months and the normal healthy male mice aged 3, 5 and 9 months. Multiple hepatic nodules and hepatic tumors were found in the liver tissues of H-ras12V transgenic male mice aged 5 and 9 months, respectively. The proportions of B lymphocytes （slgM＋CD23＋ and slgM＋B220＋ subtypes） in peripheral white blood cells from H-ras12V transgenic male mice aged 3, 5 and 9 months were significantly decreased as compared with that of non-transgenic mice （all P 〈 0.01）. The proportions of activated B lymphocytes （CD19＋CD69＋） were also significantly reduced in H-ras12V transgenic male mice at ages of 5 and 9 months （both P 〈 0.05）. Additionally, the proportions of overall and activated B lymphocytes in H-ras12V transgenic male mice were decreased gradually with age increased. For T lymphocytes, no significant differences were detected in proportions of T lymphocytes （CD3e＋） and activated T lymphocytes （CD3e＋CD69＋ and CD3e＋CD25＋） between transgenic and non-transgenic mice aged 3 and 5 months （both P 〉 0.05）. However, the overall and activated T lymphocytes were significantly decreased in H-ras12V transgenic male mice aged 9 months as compared with those in non-transgenic mice （both P 〈 0.05）. Conclusion： The

关 键 词：肝肿瘤 实验性 动物 基因修饰 淋巴细胞 

分 类 号：R735.7[医药卫生—肿瘤]