参芪扶正注射液联合hTR反义核酸对白血病小鼠骨髓细胞端粒酶活性及凋亡的影响  

Effect of Shenqi Fuzheng Injection Combined with Human Telomerase RNA Antisense on Telomerase Activity of Bone Marrow Cells and Apoptosis of Leukemic Cells in Mice

作　　者：肖扬[1] 钱玉红[1] 李力[1] 庞妍[1] 蒋祖军[1] 李勇华[1] 

机构地区：[1]广州军区广州总医院血液科,广州510010

出　　处：《中药新药与临床药理》2011年第5期505-510,共6页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：广东省自然科学基金资助项目(04300902;5000138);国家自然科学基金项目(30900645)

摘　　要：目的观察参芪扶正注射液联合hTR反义核酸对急性白血病小鼠骨髓细胞端粒酶活性及细胞凋亡的影响。方法选取近交系8～12周龄DBA-2雄性小鼠尾静脉注射L1210淋巴细胞白血病株建立白血病小鼠模型,随机分为空白对照组及治疗组,治疗组分别给予参芪扶正注射液、参芪联合放射、参芪联合hTR反义核酸、参芪联合hTR反义核酸及放射治疗,疗程结束后活杀部分小鼠,采用端粒重复扩增(TRAP)-ELISA方法检测治疗后小鼠骨髓细胞的端粒酶活性,采用AnnexinV-FITC及PI双染,FACScan流式细胞术定量检测细胞凋亡率,观察各组小鼠骨髓细胞端粒酶活性、细胞凋亡率的变化。结果成功建立L1210/DBA-2白血病小鼠模型,检测到白血病小鼠的骨髓细胞端粒酶活性较正常小鼠明显升高,细胞凋亡率较正常小鼠下降;经参芪扶正注射液以及联合治疗后,各组小鼠骨髓细胞端粒酶活性明显下降,细胞凋亡率升高,以参芪联合hTR反义核酸及放射治疗组疗效最为显著,与其他各组相比,差异有统计学意义(P<0.05)。结论急性白血病骨髓细胞端粒酶活性高表达可能是其治疗的靶点;参芪扶正注射液联合hTR反义核酸可通过下调端粒酶活性水平,促进白血病细胞的凋亡,对白血病小鼠放疗有一定增敏效应。Objective To observe the effect of Shenqi Fuzheng Injection（SFI） combined with human telomerase RNA （hTR） antisense on telomerase activity of bone marrow cells and apoptosis of leukemic cells in mice. Methods Inbreeding DBA-2 male mice aged 8-12 weeks were given injection of lymphocytes leukemia L1210 strain into the caudal vein to establish leukemia mice model. The mice were randomly divided into blank control group and treatment groups. The mice in the treatment groups were given SFI, SFI ＆ radiotherapy, SFI ＆ hTR antisense, SFI ＆ hTR antisense ＆ radiotherapy, respectively. After treatment, the telomerase activity was detected by telomerase repeat amplification protocol and enzyme-linked immunosorbent assay（ELISA） kit, cell apoptosis was observed by morphological methods of AnnexinV-FITC and PI staining, and the apoptotic rate was determined by flow eytometry. Results L1210/DBA-2 leukemia mice model had been established successfully, and higher telomerase activity ＆ lower apoptotic ,＇ate were detected in leukemia mice compared with those in normal mice. After treatment, telomerase activity was decreased, apoptotic rate was increased in the treatment groups, and the effect was the strongest in the group of SFI ＆ hTR antisense ＆ radiotherapy（P 〈 0.05, compared with other treatment groups）. Conclusion High expression of telomerase activity in bone marrow cells may be the therapeutic target for acute leukemia. SFI ＆ hTR antisense pronote the susceptibility of leukemic cells to irradiation significantly through inhibiting telomerase activity and promoting apoptosis of leukemic cells.

关 键 词：参芪扶正注射液 hTR反义核酸 白血病 端粒酶 凋亡 

分 类 号：R285.5[医药卫生—中药学]