Modified Sijunzi Granules Exhibit Hemostatic Effect by Activating Akt and Erk Signal Pathways via Regulating 5-HT and Its Receptors Levels  

作　　者：WANG Jun ZHANG Xue-ying KANG Yan-hong ZHANG Yun CHEN Xin-yi ZHOU Jia-li MA Wei 

机构地区：[1]Department of Hematology,the First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou 310006,China [2]Department of Hemato-Oncology,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China [3]Hunter Biotechnology,Inc.,Hangzhou 310051,China

出　　处：《Chinese Journal of Integrative Medicine》2024年第12期1121-1127,共7页中国结合医学杂志（英文版）

基　　金：Supported by Natural Science Foundation of Zhejiang Province(No.LQ23H270001)。

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(6μmol/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 500μg/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 of5-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 the55.6,167,and 500μg/mL dose of MSG,respectively,in which 55.6 and 167μg/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 55.6μg/mL(54%)and 167μg/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.

关 键 词：modified Sijunzi Granules Chinese medicine primary immune thrombocytopenia zebrafish 5-HYDROXYTRYPTAMINE 5-hydroxytryptamine receptor mitogen-activated protein kinase/extracellular regulated protein kinases signal pathway phosphoinositide3-kinases/protein kinase B signal pathway 

分 类 号：R285[医药卫生—中药学]