复方砷剂对骨髓增生异常综合征小鼠的疗效与安全性评价及对肠道菌群的影响  

Efficacy and safety of compound arsenic trioxide in mice with myelodysplastic syndrome and its effect on intestinal flora

作　　者：陶雨晨 陆嘉惠[2] 王冬琴[1] 任建业 管宇[1] 薛婷婷 胡可心 董孝杰 徐皓 王艳璐 TAO Yu-chen;LU Jia-hui;WANG Dong-qin;REN Jian-ye;GUAN Yu;XUE Ting-ting;HU Ke-xin;DONG Xiao-jie;XU Hao;WANG Yan-lu(Shanghai Municipal Hospital of Traditional Chinese Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200071,China)

机构地区：[1]上海中医药大学附属市中医医院,上海200071 [2]上海中医药大学附属市中医医院血液病科

出　　处：《中华中医药杂志》2022年第5期2541-2547,共7页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金面上项目(No.81873286);上海市优秀学术带头人计划(No.20XD1403500);上海市卫生系统优秀人才培养计划项目(No.2018BR15);上海市科学技术委员会医学创新研究专项重大项目(No.21Y31920400);上海申康医院发展中心临床科技创新项目(No.SHDC12020128)。

摘　　要：目的:观察复方砷剂对骨髓增生异常综合征(MDS)小鼠的疗效、安全性及对肠道菌群的影响,为MDS“虚毒并治”临床策略的生物学诠释提供科学依据。方法:选取15只雄性NUP98-HOXD13转基因小鼠分为模型组、雄黄组和复方砷剂组,5只其同源的雄性野生型C57BL/6J小鼠为阴性对照组,阴性对照组和模型组给予0.5%的羧甲基纤维素钠溶液灌胃,其余2组分别给予水飞雄黄、复方砷剂(三子黄石方)灌胃。治疗前后采集外周血进行血细胞分析,治疗后采血进行生化指标、电解质检测;治疗结束后采集小鼠粪便,提取肠道菌群DNA,于Illumina MiSeq测序平台进行V3—V4区进行双端测序及生物信息学分析。结果:与模型组比较,雄黄组与复方砷剂组小鼠外周血象显著提升(P<0.05,P<0.01),治疗组均无明显肝肾功能损害和电解质紊乱;肠道菌群测序结果显示,各组小鼠肠道菌群主要由拟杆菌门(Bacteroidetes)和厚壁菌门(Firmicutes)占主导地位,雄黄组拟杆菌门的相对丰度较模型组显著升高,厚壁菌门的相对丰度较模型组降低(P<0.05);复方砷剂组与阴性对照组接近。结论:雄黄和复方砷剂均能改善小鼠外周血象,复方砷剂还可保护菌群降低雄黄的杀伤作用,恢复肠道菌群的多样性,更大限度发挥治疗MDS的作用。Objective:To observe the efficacy and safety of compound arsenic trioxide in mice with myelodysplastic syndrome(MDS)and its effect on intestinal flora,so as to provide scientific basis for the biological interpretation of the clinical strategy of treating MDS with the combination of deficiency and toxin.Methods:Fifteen male NUP98-HOXD13 transgenic mice were divided into a model group,a realgar group and a compound arsenic agent group and five male homologous C57BL/6J wild mice were selected as a negative control group.The negative control group and the model group were intragastrically administered with 0.5%sodium carboxymethylcellulose solution,and the other two groups were intragastrically administered with the realgar,compound arsenic agent(Sanzi Huangshi Formala),respectively.The peripheral blood was collected before and after treatment for blood cell analysis,biochemical indicators and electrolyte detection.The feces were collected after treatment and the intestinal flora DNA was extracted.The V3 to V4 regions were double-ended sequenced and analyzed for trustworthiness on the Illumina MiSeq sequencing platform.Results:Compared with the model group,realgar and compound arsenic trioxide significantly improved peripheral hemogram of MDS transgenic mice(P<0.05,P<0.01),without obvious liver and kidney function damage and electrolyte disturbance.The results of intestinal flora sequencing showed that the intestinal flora of mice in each group was mainly dominated by Bacteroides and Firmicutes.The relative abundance of Bacteroides in the realgar group was higher than that in the model group,and that of Firmicutes was lower than that in the model group,with a statistically significant difference(P<0.05).Compound arsenic agent group was close to negative control group.Conclusion:Both realgar and compound arsenic can improve peripheral hemogram of mice.The compound arsenic can also protect flora,reduce the killing effect of realgar,restore the diversity of intestinal flora,and exert the effect of treating MDS to the g

关 键 词：骨髓增生异常综合征 虚毒并治 复方砷剂 肠道菌群 雄黄 髓毒劳 三子黄石方 补虚解毒 

分 类 号：R285.5[医药卫生—中药学]