摘要
目的:探讨益髓生血汤调节Notch信号通路对再生障碍性贫血(AA)小鼠骨髓造血功能的影响机制。方法:将60只CByB6F1小鼠随机分为空白组、模型组、阳性对照(CsA)组、中药复方益髓生血汤低剂量(YSSX-L)组和高剂量(YSSX-H)组,每组12只。除空白组外,其余各组小鼠给予5 Gy X射线辐照联合尾静脉输注淋巴细胞,建立免疫介导的AA小鼠模型。益髓生血汤低、高剂量组分别给予益髓生血汤8.6、17.2 g(/kg∙d)灌胃,模型组和空白组给予等体积生理盐水灌胃,阳性对照组给予环孢素25 mg(/kg∙d)灌胃,连续给药14 d。检测小鼠外周血中白细胞数(WBC)、红细胞数(RBC)、血红蛋白(Hb)、血小板数(PLT)及骨髓有核细胞数,观察小鼠骨髓病理变化检测外周血清IFN-γ、IL-4、IL-5含量,并测定脾脏组织中T淋巴细胞转录因子T-bet、GATA3、RORγt、FOXP3 mRNA和蛋白以及Notch信号通路相关基因和蛋白表达水平。结果:与空白组比较,模型组外周血WBC、RBC、Hb、PLT、骨髓有核细胞数、血清IL-4、IL-5及脾脏组织GATA3、FOXP3 mRNA和蛋白表达明显降低(P<0.01),血清IFN-γ、脾脏组织T-bet、RORγt mRNA和蛋白以及Notch1、Jagged1、DLL4 mRNA和蛋白表达明显升高(P<0.05)。与模型组比较,各干预组小鼠外周血WBC、RBC、Hb、PLT、骨髓有核细胞数、血清IL-4、IL-5及脾脏组织GATA3、FOXP3 mRNA和蛋白表达明显升高(P<0.05),血清IFN-γ以及脾脏组织T-bet、RORγt mRNA和蛋白以及Notch1、Jagged1、DLL4 mRNA和蛋白表达明显降低(P<0.05)。结论:益髓生血汤可改善AA小鼠骨髓造血功能,调节免疫紊乱,其作用机制可能与调控Notch信号通路有关。
Objective:To investigate the effects of Yisui Shengxue Decoction on the regulation of Notch signaling pathway on bone marrow hematopoiesis in mice with aplastic anemia(AA).Methods:A total of 60 CByB6F1 mice were randomly divided into blank group,model group,positive control cyclosporine(CsA)group,low-dose(YSSX-L)group and high-dose(YSSX-H)group of Chinese herbal compound Yisui Shengxue Decoction,with 12 mice in each group.Except for the blank group,the mice in each group were given 5 Gy X-ray irradiation combined with tail vein infusion of lymphocytes to establish the immune-mediated AA mouse model.The low and high dose groups were given 8.6 and 17.2 g(/kg∙d)of Yisui Shengxue Decoction by gavage,the model group and the blank group were given equal volume of saline by gavage,and the positive control group was given 25 mg(/kg∙d)of cyclosporine by gavage for 14 days.The mice were tested for white blood cell count(WBC),red blood cell count(RBC),hemoglobin(Hb),platelet count(PLT)and bone marrow nucleated cell count in peripheral blood,bone marrow pathological changes and the levels of IFN-γ,IL-4 and IL-5 in peripheral serum,and T-lymphocyte transcription factors T-bet,GATA3,RORγt,FOXP3 mRNA and protein in spleen tissues,as well as the expression levels of Notch signaling pathway-related genes and protein in spleen tissues.Results:Compared with the blank group,the peripheral blood WBC,RBC,Hb,PLT,bone marrow nucleated cell count,expressions of serum IL-4,IL-5 and spleen tissue GATA3,FOXP3 mRNA and protein were significantly lower in the model group(P<0.01),and the expressions of serum IFN-γ,spleen tissue T-bet,RORγt mRNA and protein,and Notch1,Jagged1,DLL4 mRNA and protein were significantly increased(P<0.05).Compared with the model group,peripheral blood WBC,RBC,Hb,PLT,bone marrow nucleated cell count,expressions of serum IL-4,IL-5 and spleen tissue GATA3,FOXP3 mRNA and protein were significantly higher in each intervention group(P<0.05),and the expression of serum IFN-γ and spleen tissue T-bet,RORγt mRNA and protein as well as Notch1,Jagged1,DLL4 mRNA and protein were significantly reduced(P<0.05).Conclusion:Yisui Shengxue Decoction can improve bone marrow hematopoietic function and regulate immune disorders in AA mice,and its mechanism of action may be related to the regulation of Notch signaling pathway.
作者
王雅娟
崔雯
薛征
王江丽
沈世平
韩兆鹏
胡明格
周丽丽
周欢
WANG Yajuan;CUI Wen;XUE Zheng;WANG Jiangli;SHEN Shiping;HAN Zhaopeng;HU Mingge;ZHOU Lili;ZHOU Huan(Shanxi University of Traditional Chinese Medicine,Taiyuan 030024,China;Shanghai Hospital of Traditional Chinese Medicine Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200071,China)
出处
《中国免疫学杂志》
北大核心
2025年第9期2207-2213,共7页
Chinese Journal of Immunology
基金
上海市进一步加快中医药传承创新发展三年行动计划[ZY(2021-2023)-0206-04]
上海市科学技术委员会科研计划项目(18401903700)
上海市科学技术委员会2020年度科技创新行动计划“扬帆计划”(20YF1446000)。
关键词
再生障碍性贫血
益髓生血汤
骨髓造血
免疫调节
Aplastic anemia
Yisui Shengxue Decoction
Bone marrow hematopoiesis
Immune regulation
作者简介
王雅娟,女,硕士,主要从事小儿肺病、脑病、血液病的研究,E-mail:Wangyajuan9595@163.com;通信作者:薛征,女,博士,主任医师,教授,主要从事小儿肺病、脑病、血液病的研究,E-mail:xz695@163.com。
