雷公藤红素对人急性早幼粒细胞白血病SCID小鼠移植瘤模型凝血功能的影响
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摘要
目的观察雷公藤红素对人急性早幼粒细胞白血病重度联合免疫缺陷(SCID)小鼠移植瘤模型凝血功能的影响。方法 SCID beige小鼠30只,将其中20只采用尾静脉注射对数生长期的NB4细胞5×106个/只的方法建立人急性早幼粒细胞白血病SCID小鼠移植瘤模型,并随机均分为模型组和实验组,各10只。另10只不造模作为对照组。3周后实验组腹腔注射雷公藤红素治疗14 d,对照组和模型组腹腔注射生理盐水对照。观察治疗前后3组小鼠外周血涂片中人早幼粒细胞阳性率、外周血白细胞数及凝血指标并统计生存时间。结果实验组治疗后外周血白细胞计数和人早幼粒细胞阳性率较治疗前和模型组降低、生存时间延长(P <0.05);凝血指标中凝血时间(CT)、出血时间(BT)和凝血激活酶时间(APTT)均延长(P <0.05),D-二聚体(DD)、纤维蛋白原(FIB)和内、外源性凝血因子Xa降低(P <0.05),与模型组和治疗前比较差异均有统计学意义。结论雷公藤红素可明显改善人急性早幼粒细胞白血病凝血功能,延长小鼠生存时间。
Objective: To observe the effect of tripterine on coagulation function in mice Xenograft model with SCID and acute promyelocytic leukemia(APL). Methods: Among 30 SCID beige mice,20 were used to establish Xenograft model with SCID and APL,and randomly divided into the experimental group and the model group,the other 10 as the control group. 3 weeks later,the experimental group was injected with tripterine for 14 days. The other two groups were injected with saline. The positive rate of human promyelocytes,the number of white blood cells and coagulation index in peripheral blood smears of three groups were observed before and after treatment,and the survival time was counted. Results: The white blood cell count and the positive rate of human promyelocyte in the experimental group were lower than those before treatment and those in the model group,and the survival time was prolonged(P < 0.05);coagulation time(CT),bleeding time(BT) and activated partial thromboplastin time(APTT) were prolonged(P < 0.05). D-Dimer(DD),fibrinogen(FIB) and endogenous/exogenous coagulation factor Xa decreased(P < 0.05). compared with the model group and before treatment,the difference was statistically significant. Conclusion: Tripterine can significantly improve coagulation function and prolong the survival time of mice with human APL.
Objective: To observe the effect of tripterine on coagulation function in mice Xenograft model with SCID and acute promyelocytic leukemia(APL). Methods: Among 30 SCID beige mice,20 were used to establish Xenograft model with SCID and APL,and randomly divided into the experimental group and the model group,the other 10 as the control group. 3 weeks later,the experimental group was injected with tripterine for 14 days. The other two groups were injected with saline. The positive rate of human promyelocytes,the number of white blood cells and coagulation index in peripheral blood smears of three groups were observed before and after treatment,and the survival time was counted. Results: The white blood cell count and the positive rate of human promyelocyte in the experimental group were lower than those before treatment and those in the model group,and the survival time was prolonged(P < 0.05);coagulation time(CT),bleeding time(BT) and activated partial thromboplastin time(APTT) were prolonged(P < 0.05). D-Dimer(DD),fibrinogen(FIB) and endogenous/exogenous coagulation factor Xa decreased(P < 0.05). compared with the model group and before treatment,the difference was statistically significant. Conclusion: Tripterine can significantly improve coagulation function and prolong the survival time of mice with human APL.
引文
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[13]李长江,陈正文.磁珠法与比浊法血凝仪用于医疗器械凝血激活酶时间试验和凝血的比较研究[J].中国医药指南,2016,14(22):9-10.
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[19]唐加明,梁国华,陈晓昀,等.雷公藤多甙诱导SCID小鼠体内HL-60细胞凋亡的研究[J].实用癌症杂志,2012,27(3):221-223.
[20] Davenport A,Frezza M,Shen M,et al. Celastrol and an EGCG pro-drug exhibit potent chemosensitizing activity in human leukemia cells[J]. Int J Mol Med,2010,25(3):465-470.
[21]王涤,赵万红,雷鸣,等.雷公藤红素对人早幼粒细胞白血病NB4细胞增殖和凋亡的影响[J].现代肿瘤医学,2013,21(3):478-82.
[22]杨小蕾.凝血酶和凝血因子Ⅹa在Meg-01细胞分化为血小板中的作用及其机制[D].青岛:青岛科技大学,2015.
[23]杨小蕾,葛梦凯,于爱平,等.凝血因子Ⅹa促进巨核细胞系Meg-01分化[J].中国实验血液学杂志,2016,24(2):519-525.
[24]苏延平,赵艳,顾伟英,等.血浆D-二聚体水平与急性白血病的预后分析[J].临床和实验医学杂志,2010,9(23):1773-1773.
[25]黄勇.雷公藤多苷联合缬沙坦对早期糖尿病肾病患者血清D-二聚体及细胞炎性因子的影响[J].河北医药,2017,39(4):557-562.
[2]方永光,成玉斌,陈楠楠,等.祛邪复正法治疗复发急性早幼粒细胞白血病临床研究[J].中国中医急症,2010,19(10):1686-1687.
[3]鞠满凯,张磊.急性早幼粒细胞白血病发病机制研究新进展[J].医学综述,2016,22(8):1477-1480.
[4]钟少东,蔡晓燕.急性早幼粒细胞白血病发病机制及治疗进展[J].安徽医药,2011,15(3):277-280.
[5]唐晓钰.初发急性白血病患者的凝血指标异常状况分析[J].实用癌症杂志,2015,30(3):460-462.
[6]蒋慧.急性早幼粒细胞白血病并发症及其处理[J].实用儿科临床杂志,2011,26(15):1153-1155.
[7]范晓雪,王三斌.急性早幼粒细胞白血病治疗的研究进展[J].国际输血及血液学杂志,2017,40(3):228-230.
[8]冯玉虎.急性早幼粒细胞白血病的治疗进展[J].实用医学杂志,2017,3(13):2073-2075.
[9]孙中华,郝艳梅,李玉云,等.血栓与止血分子标志物监测在急性白血病诊治中的研究进展[J].国际检验医学杂志,2014,35(5):584-586.
[10]杨京,张晓玲,马世平,等.雷公藤红素抗白血病作用研究进展[J].药学与临床研究,2016,24(3):248-252.
[11] Uttarkar S,DasséE,Coulibaly A,et al. Targeting acute myeloid leukemia with a small molecule inhibitor of the Myb/p300 interaction[J]. Blood,2016,127(9):1173-1182.
[12]刘雁峰,张梅,程小岩,等.应用NB4细胞株建立SCID beige小鼠急性早幼粒细胞白血病病理模型[J].中国实验血液学杂志,2015,23(1):50-54.
[13]李长江,陈正文.磁珠法与比浊法血凝仪用于医疗器械凝血激活酶时间试验和凝血的比较研究[J].中国医药指南,2016,14(22):9-10.
[14]戴红伟,周娇.槲皮素对急性淋巴细胞白血病模型小鼠凝血功能的影响[J].中国中医急症,2018,22(6):1349-1354.
[15]周学慧,薛华,于明华,等.中国医学科学院血液学研究所1985~2005年门诊急性白血病患者资料分析[J].临床血液学杂志,2006,19(2):76-79.
[16]福建省医学会血液学分会临床协作组.福建省2010年成人急性白血病的发病情况调查[J].中华血液学杂志,2012,33(11):902-905.
[17]吕琳琳.急性早幼粒细胞白血病出血与血栓形成机制[J].血栓与止血学,2013,19(1):41-43.
[18]陈雷,梅建刚,裘旭华,等.治疗相关性急性早幼粒细胞白血病的临床及实验室特征(附1例报告)[J].现代肿瘤医学,2014,22(6):1427-1429.
[19]唐加明,梁国华,陈晓昀,等.雷公藤多甙诱导SCID小鼠体内HL-60细胞凋亡的研究[J].实用癌症杂志,2012,27(3):221-223.
[20] Davenport A,Frezza M,Shen M,et al. Celastrol and an EGCG pro-drug exhibit potent chemosensitizing activity in human leukemia cells[J]. Int J Mol Med,2010,25(3):465-470.
[21]王涤,赵万红,雷鸣,等.雷公藤红素对人早幼粒细胞白血病NB4细胞增殖和凋亡的影响[J].现代肿瘤医学,2013,21(3):478-82.
[22]杨小蕾.凝血酶和凝血因子Ⅹa在Meg-01细胞分化为血小板中的作用及其机制[D].青岛:青岛科技大学,2015.
[23]杨小蕾,葛梦凯,于爱平,等.凝血因子Ⅹa促进巨核细胞系Meg-01分化[J].中国实验血液学杂志,2016,24(2):519-525.
[24]苏延平,赵艳,顾伟英,等.血浆D-二聚体水平与急性白血病的预后分析[J].临床和实验医学杂志,2010,9(23):1773-1773.
[25]黄勇.雷公藤多苷联合缬沙坦对早期糖尿病肾病患者血清D-二聚体及细胞炎性因子的影响[J].河北医药,2017,39(4):557-562.