【摘要】：目的:本研究旨在建立穩(wěn)定、有效、重復(fù)性好的人急性早幼粒白血病重度聯(lián)合免疫缺陷(SCID)小鼠移植瘤模型,觀察模型的病程特點(diǎn)和生物學(xué)行為。方法:將3-5周齡SCID beige小鼠隨機(jī)分為實(shí)驗(yàn)組和對(duì)照組;實(shí)驗(yàn)組鼠尾靜脈注射對(duì)數(shù)生長(zhǎng)期的NB4細(xì)胞5×106個(gè)/只,動(dòng)態(tài)監(jiān)測(cè)小鼠外周血白細(xì)胞數(shù)和外周血涂片中人早幼粒細(xì)胞陽(yáng)性率;應(yīng)用形態(tài)學(xué)和組織病理學(xué)方法確認(rèn)白血病細(xì)胞浸潤(rùn)肝、脾、肺、腎、腦等器官情況,Western blot檢測(cè)組織中PML-RARa融合蛋白表達(dá)情況。結(jié)果:接種NB4細(xì)胞2周內(nèi)的實(shí)驗(yàn)組SCID小鼠外周血白細(xì)胞計(jì)數(shù)與對(duì)照組相比差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05);同時(shí),血涂片姬姆薩染色后鏡檢未見(jiàn)到NB4細(xì)胞;接種第21天和第28天實(shí)驗(yàn)組SCID小鼠外周血白細(xì)胞計(jì)數(shù)分別為(4.79±1.13)×109/L和(7.62±2.24)×109/L,顯著高于對(duì)照組(P0.05);血涂片吉姆薩染色后可見(jiàn)NB4細(xì)胞比例分別占(2.14±0.63)%和(6.6±2.76)%;形態(tài)學(xué)觀察顯示,接種21 d后實(shí)驗(yàn)組SCID小鼠體內(nèi)出現(xiàn)單個(gè)或多個(gè)腫瘤實(shí)體包塊;同時(shí),組織切片HE染色表明,肝、脾、肺、腎、腦組織均有不同程度的瘤細(xì)胞浸潤(rùn);細(xì)胞免疫熒光結(jié)果顯示,實(shí)驗(yàn)組小鼠骨髓細(xì)胞CD33表達(dá)呈陽(yáng)性(P0.05);Western blot數(shù)據(jù)證實(shí),肝、腎、腦組織中檢測(cè)到不同水平的PML-RARa融合蛋白表達(dá)。結(jié)論:SCID小鼠鼠尾靜脈注射NB4細(xì)胞可成功構(gòu)建人急性早幼粒細(xì)胞白血病小鼠模型,該模型能模擬臨床白血病累及骨髓和彌漫生長(zhǎng)特點(diǎn),是研究人類白血病發(fā)病機(jī)理及實(shí)驗(yàn)治療的良好模型。
[Abstract]:Objective: to establish a stable, effective and reproducible human acute promyelocytic leukemia severe combined immunodeficient (SCID) mouse model, and to observe the course of disease and biological behavior of the model. Methods: SCID beige mice aged 3 to 5 weeks were randomly divided into experimental group and control group. In the experimental group, 5 脳 10 ~ 6 NB4 cells were injected intravenously into the tail vein to dynamically monitor the number of peripheral blood leukocytes and the positive rate of human progranulocytes in peripheral blood smears. The expression of PML-RARa fusion protein in leukemic cells infiltrated into liver, spleen, lung, kidney and brain was detected by morphology and histology., Western blot was used to detect the expression of PML-RARa fusion protein in liver, spleen, lung, kidney, brain and other organs. Results: there was no significant difference in peripheral blood leukocyte count between the experimental group and the control group within 2 weeks after inoculated with NB4 cells (P 0.05). At the same time, no NB4 cells were found in the blood smear after Giemsa staining. On the 21st and 28th day of vaccination, the peripheral blood leukocyte counts of SCID mice in the experimental group were (4.79 鹵1.13) 脳 109 脳 L and (7.62 鹵2.24) 脳 109 / L, respectively, which were significantly higher than those in the control group (P 0.05). The percentage of NB4 cells in blood smears was (2.14 鹵0.63)% and (6.6 鹵2.76)%, respectively, and the morphological observation showed that one or more tumor solid masses appeared in SCID mice in the experimental group 21 days after vaccination, and the percentage of DNA cells in the experimental group was (2.14 鹵0.63)% and (6.6 鹵2.76)%, respectively. At the same time, HE staining showed that there were different degrees of tumor cell infiltration in liver, spleen, lung, kidney and brain tissue, and the results of cellular immunofluorescence showed that the expression of CD33 in bone marrow cells of the experimental group was positive (P 0.05). Western blot data confirmed that different levels of PML-RARa fusion protein expression were detected in liver, kidney and brain tissue. Conclusion: the mouse model of human acute promyelocytic leukemia can be successfully established by injecting NB4 cells into the tail vein of SCID mice. The model can simulate the characteristics of clinical leukemia involving bone marrow and diffused growth. It is a good model to study the pathogenesis and experimental treatment of human leukemia.
【作者單位】： 西安交通大學(xué)醫(yī)學(xué)院第一附屬醫(yī)院血液內(nèi)科;
【基金】：陜西省科技統(tǒng)籌創(chuàng)新工程計(jì)劃項(xiàng)目(2012KTCL03-12)
【分類號(hào)】：R733.7;R-332

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