摘要Objective:To investigate the hemostatic effect of modified Sijunzi Granules(MSG)in primary immune thrombocytopenia(ITP)zebrafish model and explore the potential mechanism.Methods:AB strain wild type zebrafish were treated with simvastatin(6 μ mol/L)for 24 h to establish the hemorrhage model(model control group).The zebrafish were treated with MSG at different doses(55.6,167,and 500 μg/mL),respectively.The hemostatic effect was assessed by examining the intestinal bleeding and hemostatic rate.5-hydroxytryptamine(5-HT)content was determined using enzyme-linked immunosorbent assay(ELISA)assay.The expressions of 5-HT2aR,5-HT2bR,and SERT genes were detected by quantitative real-time polymerase chain reaction(PCR).The protein expressions of protein kinase B(Akt),p-Akt,extracellular regulated protein kinases(Erk),and p-Erk were examined using Western blot analysis.Results:The intestinal bleeding rate was 37％,40％,and 80％in the 55.6,167,and 500 μ g/mL dose of MSG,respectively,in which 55.6 and 167 μ g/mL MSG dose groups were associated with significantly decreased intestinal bleeding rate when compared with the model control group(70％,P＜0.05).Significantly higher hemostatic rates were also observed in the 55.6 μg/mL(54％)and 167 μg/mL(52％)MSG dose groups(P＜0.05).MSG increased the 5-HT content and mRNA expression levels of 5-HT2aR,5-HT2bR,and SERT(P＜0.05).In addition,caspase3/7 activity was inhibited(P＜0.05).Significant increase in p-Akt and p-Erk was also detected after treatment with MSG(P＜0.05).Conclusions:MSG could reduce the incidence and severity of intestinal bleeding in zebrafish by activating MAPK/Erk and PI3K/Akt signal pathways through regulating the levels of 5-HT and its receptors,which may provide evidence for the treatment of ITP.