基于JAK2-STAT信号通路探讨升血小板胶囊通过巨核细胞对ITP的治疗作用  

Based on the JAK2-STAT Signaling Pathway to Explore the Therapeutic Effect of Sheng Xuexiaoban Capsules on ITP Through Megakaryocytes

作　　者：房丽君 郭旭彪 高红旭 白瑞涛 董焕 白恩会 杨文华[1,2] 史哲新 Fang Lijun;Guo Xubiao;Gao Hongxu;Bai Ruitao;Dong Huan;Bai Enhui;Yang Wenhua;Shi Zhexin(Department of Hematology,First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China;National Clinical Research Center for Chinese Medicine Acupuncture and Moribustion,Tianjin 300193,China;Institute of Hematology,Hematology Hospital,Chinese Academy of Medical Sciences,Tianjin 300020,China)

机构地区：[1]天津中医药大学第一附属医院血液科,天津300193 [2]国家中医针灸临床医学研究中心,天津300193 [3]中国医学科学院血液病医院血液学研究所,天津300020

出　　处：《南开大学学报（自然科学版）》2023年第5期16-22,42,共8页Acta Scientiarum Naturalium Universitatis Nankaiensis

基　　金：国家自然科学基金青年项目(82104618);升血小板胶囊双向调节机体免疫的基础研究。

摘　　要：巨核细胞增生不良及血小板释放障碍在免疫性血小板减少症(ITP)中的致病作用日趋突显,并作为该病的治疗靶点而被广泛研究.升血小板胶囊在临床上可有效提高ITP患者的血小板数量,但作用机制未知.用升血小板胶囊悬液通过灌胃处理Bal/c小鼠14 d,再腹腔注射CD41单抗造ITP模型并观察血小板回升情况.通过病理切片、流式分析、分选、RT-PCR、RNA-seq等技术分析升血小板胶囊对巨核细胞增殖及血小板释放的作用.结果表明,升血小板胶囊治疗组的ITP模型鼠血小板回升速度显著高于对照组;巨核细胞数量及血小板释放相关凋亡蛋白表达增加;应用血小板生成素(TPO)受体及I型干扰素表达增加;JAK2-STAT信号通路被显著激活,均可促进巨核细胞增殖及血小板释放.本研究证明升血小板胶囊可以通过JAK2-STAT信号通路增加巨核细胞数量、促进巨核细胞血小板释放治疗ITP.The pathogenic role of megakaryocyte dysplasia and platelet release disorder in ITP has become increasingly prominent and has been widely studied as the therapeutic target of the disease.Sheng Xuexiaoban capsules can effectively increase the number of platelets in patients with ITP clinically,but the mechanism behind it is unknown.In this study,the mechanism of Sheng Xuexiaoban capsules in treating ITP through megakaryocytes was futher explored using an ITP animal model,cell experiments,and molecular biology experiments.An ITP model was established in Bal/c mice by intragastric administration of Sheng Xuexiaoban capsules for 14 d,followed by intraperitoneal injection of anti-CD41 monoclonal antibody to induce ITP.Platelet recovery was observed.The effects of Sheng Xuexiaoban capsules on megakaryocyte proliferation and platelet production were tested using HE staining pathology,flow cytometry,flow cell sorting,RT-PCR,and RNA-seq.The platelet recovery rate in ITP model mice treated with Sheng Xuexiaoban capsules was significantly higher than that in the control group.The number of mega karyocytes and the expression of apoptosis proteins related to platelet release were increased.Additionally.the expression of the TPO receptor and Type I interferon also increased.The JAK2-STAT signaling pathway was significantly activated,which could promote megakaryocyte proliferation and platelet release.Conclusion:Sheng Xuexiaoban capsules can increase the number of megakaryocytes and promote the platelet release of megakaryocytes through the JAK2-STAT signaling pathway.This finding provides a theoretical basis for the drug's treatment of ITP with megakaryocyte dysfunction.

关 键 词：免疫性血小板减少症 升血小板胶囊 巨核细胞 JAK2-STAT信号通路 

分 类 号：R558[医药卫生—血液循环系统疾病]