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地黄多糖通过 HIF-1α/NF-κB 信号通路调节再生障碍性贫血小鼠骨髓微环境。

Rehmannia Glutinosa Polysaccharide Regulates Bone Marrow Microenvironment via HIF-1α/NF-κB Signaling Pathway in Aplastic Anemia Mice.

机构信息

Chongqing Hospital of Traditional Chinese Medicine, Department of Oncology, No.6, Panxi Seventh Branch Road, Jiangbei District, Chongqing, 400021, China.

Zhejiang Chinese Medical University, School of Pharmaceutical Science, No. 548, Binwen Road, Binjiang District, Hangzhou, Zhejiang Province, 311402, China.

出版信息

An Acad Bras Cienc. 2023 Aug 4;95(3):e20220672. doi: 10.1590/0001-3765202320220672. eCollection 2023.

Abstract

Aplastic anemia (AA), a rare disorder, is associated with bone marrow microenvironment (BMM). Presently, AA treatment is of great difficulty. This study aimed to explore the mechanism of action of Rehmannia glutinosa polysaccharide (RGP) in AA. Busulfan was used to induce AA in BALB/c mice; blood cell count and Ray's Giemsa staining were used to assess the severity of hematopoietic failure; HE was performed to assess the pathological state of the marrow cavity; ELISA was performed to assess IL-4, IL-10, IL-6, IL-12, IL-1β, TNF-α, MCP-1, VEGF, and EPO; and WB was performed to evaluate the effects of RGP on the HIF-1α/NF-κB signaling. Significant downregulation of hemocyte levels in the blood and nucleated cells in the bone marrow was reversed by RGP and Cyclosporine A (CA). Compared with the AA group, dilating blood sinusoids, inflammation, hematopoiesis, decreased bone marrow cells and megakaryocytes were alleviated by RGP and CA, and the HIF-1α/NF-κB signaling was inhibited too. Notably, RGP was more effective when used in combination with CA. In this study, we established a relationship between BMM and the HIF-1α/NF-κB signaling pathway and found that RGP regulates BMM by suppressing the activation of the HIF-1α/NF-κB signaling. Thus, RGP exerts a pharmacological effect on AA.

摘要

再生障碍性贫血(AA)是一种罕见的疾病,与骨髓微环境(BMM)有关。目前,AA 的治疗难度很大。本研究旨在探讨地黄多糖(RGP)在 AA 中的作用机制。采用白消安诱导 BALB/c 小鼠 AA;血细胞计数和瑞氏吉姆萨染色评估造血衰竭的严重程度;HE 评估骨髓腔的病理状态;ELISA 评估 IL-4、IL-10、IL-6、IL-12、IL-1β、TNF-α、MCP-1、VEGF 和 EPO;WB 评估 RGP 对 HIF-1α/NF-κB 信号的影响。RGP 和环孢素 A(CA)可逆转血液中血细胞水平和骨髓中有核细胞水平的显著下调。与 AA 组相比,RGP 和 CA 减轻了扩张的血窦、炎症、造血功能下降、骨髓细胞和巨核细胞减少,并抑制了 HIF-1α/NF-κB 信号。值得注意的是,RGP 与 CA 联合使用时效果更好。本研究建立了 BMM 与 HIF-1α/NF-κB 信号通路之间的关系,并发现 RGP 通过抑制 HIF-1α/NF-κB 信号的激活来调节 BMM。因此,RGP 对 AA 具有药理作用。

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