异丁酰胺活化成年小鼠中胚胎εy珠蛋白基因的转录

Isobutyrimide activate transcription of embryonic εy globin gene in adult mice

实验自己合成的异丁酰胺对小鼠活体内胚胎珠蛋白基因转录的影响。在以每天500～900mg／kg体重的剂量注射15天后，鼠胚胎εymRNA水平可达到未注射对照的3～6倍。受注射小鼠的血红蛋白浓度（HGB）、红细胞计数（RBC）、红细胞压积（HCT）及白细胞计数（WBC）基本上均在正常范围内。受注射家兔的血液钾、钠、氯含量无异常变化，血浆离子渗透压亦保持稳定。这些结果说明异丁酰胺能够有效地在成年小鼠体内作用于早期成红细胞，激活胚胎εy-珠蛋白基因的转录，并且不显示血液学和电解质毒性，进一步证明了其在β-地中海贫血治疗中的潜在价值。

We examined effect of isobutyrimide synthersized by ourselves,on embryonic globin gens in normal micein vivo. After 15 days' injection under the doses of 500mg ~ 900mg/(kg· d), the level of Ey mRNA could be inducedsignificantly up to 3 ~ 6 folds of the controls (εy/Mα mRNA=9% ~ 17%). The HGB, RBC, HCT, WBC parameters,derived from mice injected with different doses of butyrimide by interval of 24 hours for 2 weeks, were within thenormal range generally. In rabbits injected with isobutyrimide in the same regiment, the concareion of blood K+,Na+ and Cl- were all within normal range and serum ionic osmotic pressure remained stable as well. These resultsshow that isobutyrimide can effectively act on early stages of erythroid progenitor differentiation in adult mice andactive transcription of embryonic εy globin gene and have no hematological toxicity, suggesting the potential value ofisobutyrimide in treatment of β-thalassemia and sickle cell anemia.