端粒酶抑制剂联合辐射对小鼠骨髓造血的抑制作用  

Inhibitory Effect of Telomerase Inhibitors Combined with X-Irradiation on Bone Marrow Hematopoiesis in Mice

作　　者：阮晓峰[1] 薛明慧[1] 周云峰[2] 

机构地区：[1]湖北省襄樊市中心医院肿瘤科,襄樊441021 [2]武汉大学医学院,武汉430071

出　　处：《中国实验血液学杂志》2003年第4期363-367,共5页Journal of Experimental Hematology

摘　　要：为了探讨端粒酶抑制剂联合X线照射对荷瘤小鼠的骨髓抑制作用 ,采用正交实验设计 ,应用端粒酶抑制剂 [AZT 30 0mg/ (kg·d) ,lamivudine 15 0mg/ (kg·d) ]联合X线照射 (2Gy× 5次 / 1周 )处理移植性乳腺癌 (MA782 )小鼠 ,观察其对骨髓有核细胞、外周血像及骨髓端粒酶活性的影响。结果显示 ,未处理、单纯X线照射、单纯lamivudine和单纯AZT处理的小鼠骨髓有核细胞数 (× 10 7/股骨 )分别为 2 .1875 ,1.7375 ,1.75 0 0和 1.3475 ;AZT和X线照射均有显著减少骨髓有核细胞的作用 (P <0 .0 1) ,lamivudine也有减少骨髓有核细胞的作用 (P <0 0 5 )。未处理小组小鼠外周血白细胞升高 3.70 % ,单纯X线照射 ,单纯lamivudine和单纯AZT处理的小鼠外周血白细胞下降率分别为 18.0 9% ,16 .19%和 4 1.0 0 % ;AZT ,lamivudine和X线照射均减少小鼠外周血白细胞 (P<0 .0 5 ) ,AZT ,lamivudine ,X线照射对小鼠外周血红细胞及血小板的作用无统计学意义 (P >0 .0 5 )。未处理 ,单纯X线照射 ,单纯lamivudine和单纯AZT处理的小鼠骨髓细胞端粒酶活性分别为 1.4 98,1.4 83,0 .816和 0 72 7,AZT和lamivudine均有减少骨髓细胞端粒酶活性的作用 (P <0 .0 5 )。结论 :端粒酶抑制剂AZT和lamivudine联合X线照射有显著抑制骨髓有核细胞?The purpose of this study was to evaluate the effect of telomerase inhibitors combined with X irradiation on bone marrow hematopoiesis in tumor carrying mice. With an orthogonal experiment design, the telomerase inhibitors [azidothymidine, AZT 300 mg/(kg·day) and lamivudine 150 mg/(kg·day), per os, bid, ×2 weeks] and X irradiation [total dose 10 Gy (2 Gy×5) in 1 week] were used to treat BALB/c mice carrying breast cancer MA 782 for evaluating the influence on peripheral blood cells, bone marrow nucleated cells and telomerase activity. Telomerase activity was detected by a PCR based telomeric repeat amplification protocol (TRAP) coupled with ELISA. The results showed that the number of marrow nucleated cells (×10 7/ femur) was 2.1875 in untreated group, and 1.7375, 1.7500 and 1.3475 in irradiated, lamivudine and AZT groups, respectively, these suggested that AZT and irradiation could obviously decrease the number of marrow nucleated cells (P<0.01 or P<0.05). The peripheral WBC increased 3.7% in untreated mice, and irradiation, lamivudine and AZT reduced 18.09%, 16.19% and 41.00% of WBC, respectively (P<0.05) . Irradiation, lamivudine and AZT showed no obvious effect on RBC and platelet counts (p>0.05). The telomerase activity (A 450 nm) of marrow cells was 1.498, 1.483, 0.816 and 0.727 in untreated, irradiation, lamivudine and AZT groups, respectively. It is concluded that AZT and lamivudine combined with X irradiation inhibit bone marrow nucleate cells and the peripheral WBC, manifest inhibitory effect on telomerase activity in murine bone marrow, but have no effect on the peripheral RBC and platelet.

关 键 词：端粒酶抑制剂 叠氮胸苷 拉米夫定 X线照射 造血抑制 

分 类 号：R331.2[医药卫生—人体生理学] R979.1[医药卫生—基础医学]