JAK2/STAT3通路介导的EPO生成在改善妊娠期缺铁性贫血中的作用机制OA

Objective:To investigate the effects and mechanism of Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway-mediated erythropoietin(EPO)production on iron-defi-ciency anemia(IDA)in pregnant rats.Methods:An IDA model was first induced by feeding a low-iron diet combined with periodic phlebotomy;male and female rats were then mated to establish a gestational IDA mod-el.The pregnant rats were randomly allocated to model,pathway activator(2mg/kg coumermycin)and path-way inhibitor(5 mg/kg AG490)groups;normal pregnant rats served as the control group(n=10 per group).From 18th gestational day the respective drugs were administered to rats in each group intraperitoneally once daily for 7 consecutive days.Placental weight and fetal parameters were recorded.Hematological parameters were determined biochemically;serum iron and total iron-binding capacity(TIBC)were measured colorimet-rically.Serum hepcidin,EPO,interleukin-6(IL-6)and C-reactive protein(CRP)were quantified by ELISA.Liver histopathology was examined by HE staining;ferritin heavy chain(FTH)expression was detec-ted by immunohistochemistry,and JAK2/STAT3 pathway-related proteins were analyzed by Western blot.Results:Compared with control group,model group exhibited decreased placental weight,fetal body length and weight,Hb,HCT,RBC,MCHC,serum hepcidin,serum iron,EPO,hepatic FTH,and the ratios of p-JAK2/JAK2 and p-STAT3/STAT3(P<0.05),whereas serum TIBC,IL-6 and CRP were increased(P<0.05).Compared with the model group,the activator group showed the opposite changes in all the above in-dicators(P<0.05),whereas the inhibitor group exhibited trends that reversed those of the activator group(P<0.05).Conclusions:The JAK2/STAT3 signaling pathway may positively regulating EPO production,amel-iorating disturbed iron metabolism and attenuating inflammation,and consequently protect against maternal a-nemia and intrauterine growth restriction in pregnant rats with IDA.