【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.更多还原

【Abstract】 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 megakaryocytes 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.更多还原