【目的】观察阿胶治疗β-地中海贫血 （简称β-地贫） 患者妊娠期贫血的疗效及对早期生长反应因子2 （EGR2） 表达的影0.701、0.683 （P＜0.001） 。 【结论】基因类型为βCD41-42 （-TTCT） /βN 的地贫孕妇口服阿胶治疗效果最佳，其疗效可能与上调 EGR2表达，激活RNA聚合酶Ⅱ启动子，促进核酸结合等发挥珠蛋白基因转录调控作用有关，从而最终有效改善贫血。 响。 【方法】转录组测序 （RNA-seq） ：将20例β-地贫孕妇按3∶1比例随机分配到治疗组15例 （其中脱落1例，最终纳入14例） 和对照组5例，治疗组口服阿胶粉，对照组不予干预，疗程为4周。采集2组孕妇治疗前后的外周血进行RNA-seq分析，确 定候选靶标。随后开展前瞻性临床随机对照试验 （RCT） ：招募41例β-地贫孕妇，按3∶2比例随机分配到治疗组24例和对照 组17例，治疗组口服阿胶粉，对照组口服阿胶粉模拟剂，疗程为4周。检测2组孕妇治疗前后的血液学参数，并采用实时聚 合酶链反应 （Real-time PCR） 及蛋白免疫印迹 （Western Blotting） 法检测候选靶标的mRNA及蛋白表达量。 【结果】（1） RNA-seq 分析：基因型为βCD41-42 （-TTCT） /βN 的治疗组治疗后EGR2表达显著上调 （log2 FC=1.915；校正P值 = 9.84E-03） ，确定 EGR2为候选靶标。 （2） RCT试验：①治疗后，2组β-地贫孕妇平均血红蛋白 （Hb） 浓度变化无统计学差异 （P＞0.05） ，但基因 类型为βCD41-42 （-TTCT） /βN 的治疗组患者Hb浓度平均升高 （6.54 ± 4.74） g/L，较其他基因类型的β-地贫孕妇有显著性升高 （P＜0.05） 。②基因类型为βCD41-42 （-TTCT） /βN 的治疗组患者治疗后外周血EGR2 mRNA及蛋白表达量均显著升高 （P＜ 0.05） ；且2组β-地贫孕妇治疗前后Hb浓度差值与EGR2 mRNA及蛋白表达量差值均存在显著正相关关系，相关系数分别为

Abstract：Objective To observe the efficacy of Asini Corii Colla for the treatment of women with pregnancy anemia induced by β-thalassemia and its effect on the expression of early growth response 2 （EGR2） . Methods Transcriptome sequencing （RNA-seq） was performed firstly. Twenty pregnant women with β -thalassemia were randomly assigned to the treatment group and the control group at the proportion of 3∶1. There were 15 cases allocated to the treatment group，one case fell off during the trial，and eventually 14 cases were included. The control group had 5 cases. The treatment group was given Asini Corii Colla powder orally，and the control group had no intervention. The course of treatment covered 4 weeks. The peripheral blood of the two groups of pregnant women was sampled before and after treatment for RNA-seq analysis，and then the candidate targets were defined. Subsequently，a prospective clinical randomized controlled trial （RCT） was conducted. A total of 41 pregnant women with β -thalassemia were randomly assigned to the treatment group（24 cases） and the control group （17 cases） at the proportion of 3∶2. The treatment group was treated with Asini Corii Colla powder orally，and the control group was treated with the simulant of Asini Corii Colla Powder orally. The course of treatment covered 4 weeks. The hematological parameters of the two groups of pregnant women were detected before and after treatment，and the mRNA and protein expression levels of candidate targets were detected by real-time polymerase chain reaction （real-time PCR） and western blotting respectively. Results （1）The results of RNA-seq analysis showed that EGR2 expression of patients with genotype βCD41-42（-TTCT） /βN in the treatment group was significantly up-regulated after treatment （log2 FC=1.915； Padj =9.84E-03）， and EGR2 was named as the candidate target. （2） The results of RCT showed that after treatment，there was no significant difference in the average hemoglobin （Hb） concentration between the two groups of pregnant women with β-thalassemia （P＞0.05） ， but the average Hb of the patients with genotype βCD41-42 （-TTCT） /βN in the treatment group increased by （6.54±4.74） g/L， which was significantly higher than that of other genotypes of pregnant women with β-thalassemia（P＜0.05） . The expression levels of EGR2 mRNA and protein in peripheral blood of the patients with genotype βCD41-42（-TTCT） /βN in the treatment group were significantly increased after treatment （P＜ 0.05） . The pre- and post-treatment difference of Hb concentration in the two groups of pregnant women with β-thalassemia was positively correlated with pre- and post-treatment difference of EGR2 mRNA level and EGR2 protein level，and the correlation coefficients were 0.701 and 0.683，respectively（P＜0.001） . Conclusion The pregnant women with thalassemia of genotype βCD41-42 （-TTCT） /βN can achieve satisfactory efficacy after oral administration of Asini Corii Colla. Its curative effect for improving anemia may be related to the transcriptional regulation of globin genes through up-regulating EGR2 expression，activating RNA polymerase Ⅱ promoter，and promoting nucleic acid binding.

R271.9

国家自然科学基金资助项目 （编号：81704111）；广东省科技计划项目 （编号：2017ZC0150）