含盐酸二甲双胍联合方案治疗再生障碍性贫血的短期疗效观察  

Observations on the short-term therapeutic effects of combined therapy with metformin hydrochloride for aplastic anemia

作　　者：卢学春[1] 杨波[1] 迟小华[2] 蔡力力[3] 于睿莉[1] 刘洋[1] 刘丽宏[2] 李炳军[1] 吴晓雄[4] 李松威[4] 脱帅[5] 张峰[6] 脱朝伟[5] 姚善谦[1] 范利[7] 

机构地区：[1]解放军总医院南楼血液科,北京100853 [2]解放军第二炮兵总医院药剂科,北京100800 [3]解放军总医院南楼临检科,北京100853 [4]解放军总医院第一附属医院血液科,北京100037 [5]解放军第202医院,沈阳110003 [6]中国科学院北京基因组研究所,北京100029 [7]解放军总医院南楼心内科,北京100853

出　　处：《解放军医学杂志》2012年第3期229-233,共5页Medical Journal of Chinese People's Liberation Army

基　　金：国家科技支撑计划(2009BAI86B04);国家自然科学基金(30772597,30873086,81172986);解放军总医院科技创新苗圃基金(11KMM24,11KMM23)~~

摘　　要：目的采用临床生物信息学方法筛选治疗再生障碍性贫血(AA)的新型药物并评估其临床疗效。方法首先建立AA的人类全基因组表达谱,与药物基因组学数据库进行相似性分析,筛选可能有效的药物。纳入难治性AA患者[接受过免疫抑制剂和(或)雄激素治疗时间超过6个月无效]作为研究对象评估疗效,6个月后评估临床疗效和不良反应。结果临床生物信息学筛选结果显示盐酸二甲双胍可能对AA有治疗作用。纳入43例难治性AA患者(其中15例为重型AA),采用包含盐酸二甲双胍、环孢素A(CsA)和司坦唑醇的联合方案进行治疗,结果显示:27例输血依赖患者在治疗6个月后全部(100%)停止输血;40例贫血患者中,37例(92.5%)血红蛋白完全恢复正常;30例血小板低于20×109/L的患者中,28例(93.3%)升至50×109/L以上;35例白细胞低于2.5×109/L的患者中,31例(88.6%)升至3.5×109/L以上。40例贫血患者中,1例出现肾功能异常,停用环孢素A后恢复正常;18例出现转氨酶升高,加用保肝药物并减少司坦唑醇用量后恢复正常。所有患者均未出现低血糖反应。结论盐酸二甲双胍、环孢素A和司坦唑醇联合方案治疗难治性AA有效。Objective This paper aims to screen and select new drugs with potential in the treatment of aplastic anemia,and to evaluate their clinical efficacy through clinical bioinformatics methods.Methods First,we established genome expression profiles of aplastic anemia（AA） patients,and conducted similarity analyses with the pharmacogenomics database to screen and select drugs with possible efficacy.Intractable AA patients who received immunosuppressors and/or androgen for more than six months showing no clinical efficacy were included for the study to evaluate therapeutic effects of the therapeutic regime for the study.Clinical efficacy and adverse effects were evaluated after six months.Results The clinical bioinformatics results showed that metformin hydrochloride may have therapeutic effects on AA.Forty-three intractable AA patients（15 with severe AA） were treated with metformin hydrochloride therapy combined with cyclosporin A（CsA） and stanozolol.The results showed that all the 27 transfusion-dependent patients（100%） became transfusion independent after a 6-month therapy.The hemoglobin level completely returned to normal in 37 out of 40 anemia patients（92.5%）.Among 40 patients with platelet counts lower than 20×10^9/L,the platelet count of 28 patients（90.3%） increased to higher than 50×10^9/L.The white cell count increased to higher than 3.5×10^9/L in 30 out of 35 patients（88.6%） with white cell counts lower than 2.5×10^9/L.Among 40 anaemic patients,1 was found to have abnormal renal function,but it recovered to the normal range after ending cyclosporin A treatment.Eighteen patients were found to have elevated transaminase levels which were lowered to normal range after using liver protectant and reducing the dosage of stanozolol.There were no instances of hypoglycemia among all patients throughout the treatment.Conclusion The combination of metformin hydrochloride and cyclosporine and stanozolol is effective in refractory aplastic anemia with acceptable toxicity.

关 键 词：贫血 再生障碍性 盐酸二甲双胍 血小板 白细胞 

分 类 号：R556.5[医药卫生—血液循环系统疾病]