一石二鸟：益气生血散调控骨髓细胞增殖与凋亡以缓解化疗所致骨髓抑制。
Two birds with one stone: YQSSF regulates both proliferation and apoptosis of bone marrow cells to relieve chemotherapy-induced myelosuppression.
作者信息
Zeng Miao, Zhang Yue, Zhang Xiaolu, Zhang Wenlan, Yu Qun, Zeng Wenyun, Ma Dongming, Gan Jiali, Yang Zhen, Jiang Xijuan
机构信息
School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
出版信息
J Ethnopharmacol. 2022 May 10;289:115028. doi: 10.1016/j.jep.2022.115028. Epub 2022 Jan 22.
ETHNOPHARMACOLOGICAL RELEVANCE
Yiqi Shengsui formula (YQSSF) is a commonly used formula to treat chemotherapy-induced myelosuppression, but little is known about its therapeutic mechanisms.
AIM OF THIS STUDY
This study aims to examine the effect of YQSSF in treating myelosuppression and explore its mechanism.
MATERIALS AND METHODS
A myelosuppression BALB/c mouse model was established by intraperitoneal (i.p.) injection of cyclophosphamide (CTX). The efficacy of YQSSF in alleviating chemotherapy-induced myelosuppression was evaluated by blood cell count, immune organ (thymus, spleen, liver) index, bone marrow nucleated cell (BMNC) count and histopathological analysis of bone marrow and spleen. Then, ultra-performance liquid chromatograph quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to analyze the ingredients of YQSSF extract. Key effects and potential mechanism of YQSSF extract in alleviating myelosuppression were predicted by network pharmacology method. Finally, cell cycle and TUNEL staining of bone marrow cells was detected to verify the key effects, and RT-qPCR or Western blotting were performed to measure the gene and protein expressions of the effect targets respectively to confirm the predicted mechanism of YQSSF for myelosuppression.
RESULTS
YQSSF up-regulated the number of peripheral blood leukocytes and BMNC, reduced spleen index and liver index, improved the pathological morphology of bone marrow and spleen. A total of 40 ingredients were isolated from YQSSF extract using UPLC-Q/TOF-MS analysis. Network pharmacology revealed that YQSSF regulated both proliferation and apoptosis to alleviate myelosuppression. Finally, YQSSF decreased G0/G1 ratio, increased the proportion of bone marrow cells in S phase and proliferation index (PI), and reduced apoptotic cells in femur bone marrow. RT-qPCR and Western blotting showed that YQSSF up-regulated the expression levels of CDK4, CDK6, CyclinB1, c-Myc and Bcl-2, as well as down-regulated the expression levels of Cyt-c, Fas, Caspase-8/3 and p53.
CONCLUSIONS
YQSSF promotes the proliferation and inhibits the apoptosis of bone marrow cells to relieve chemotherapy-induced myelosuppression.
民族药理学相关性
益气生髓方（YQSSF）是治疗化疗引起的骨髓抑制的常用方剂，但其治疗机制尚不清楚。
本研究目的
本研究旨在探讨YQSSF对骨髓抑制的治疗作用并探索其机制。
材料与方法
通过腹腔注射环磷酰胺（CTX）建立骨髓抑制BALB/c小鼠模型。通过血细胞计数、免疫器官（胸腺、脾脏、肝脏）指数、骨髓有核细胞（BMNC）计数以及骨髓和脾脏的组织病理学分析来评估YQSSF缓解化疗诱导的骨髓抑制的疗效。然后，采用超高效液相色谱-四极杆飞行时间质谱（UPLC-Q-TOF/MS）分析YQSSF提取物的成分。通过网络药理学方法预测YQSSF提取物缓解骨髓抑制的关键作用和潜在机制。最后，检测骨髓细胞的细胞周期和TUNEL染色以验证关键作用，并分别进行RT-qPCR或蛋白质印迹法检测效应靶点的基因和蛋白表达，以证实YQSSF对骨髓抑制的预测机制。
结果
YQSSF上调外周血白细胞和BMNC数量，降低脾脏指数和肝脏指数，改善骨髓和脾脏的病理形态。使用UPLC-Q/TOF-MS分析从YQSSF提取物中分离出共40种成分。网络药理学显示YQSSF通过调节增殖和凋亡来缓解骨髓抑制。最后，YQSSF降低G0/G1比值，增加骨髓细胞S期比例和增殖指数（PI），并减少股骨骨髓中的凋亡细胞。RT-qPCR和蛋白质印迹法显示YQSSF上调CDK4、CDK6、CyclinB1、c-Myc和Bcl-2的表达水平，同时下调Cyt-c、Fas、Caspase-8/3和p53的表达水平。
结论
YQSSF促进骨髓细胞增殖并抑制其凋亡，从而缓解化疗诱导的骨髓抑制。
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