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牛蒡苷素-缬氨酸酯对化疗引起的小鼠骨髓抑制的影响。

The effects of Arctigenin-Valine ester on chemotherapy-induced myelosuppression in mice.

机构信息

College of Chinese Medicinal Material, Jilin Agricultural University, 2888 Xincheng Street, Changchun, Jilin province 130118, China.

College of Chinese Medicinal Material, Jilin Agricultural University, 2888 Xincheng Street, Changchun, Jilin province 130118, China.

出版信息

Bioorg Med Chem. 2019 Jun 15;27(12):2480-2486. doi: 10.1016/j.bmc.2019.02.052. Epub 2019 Feb 26.

DOI:10.1016/j.bmc.2019.02.052
PMID:30837167
Abstract

OBJECTIVE

To explore whether Arctigenin-Valine ester (ARG-V) can treat myelosuppression caused by chemotherapy.

METHODS

The number of peripheral blood cells of the mice was measured by an automatic blood analyzer, and the hematopoietic progenitor colonies CFU-GM, CFU-E, BFU-E, and CFU-Meg were cultured in vitro. Hematopoietic progenitor colonies and BMNCs were counted under an inverted microscope. The expressions of cytokines GM-CSF, EPO and TPO were detected by ELISA. The cell cycle was measured by flow cytometry. The expressions of related proteins MEK and p-ERK were quantitated by western blots, and the thymus index and spleen index were quantitated.

RESULTS

After taking ARG-V, the peripheral blood cells of the mice gradually returned to normal, the number of nucleated cells in the bone marrow increased, the thymus index increased, the spleen index decreased, the number of hematopoietic progenitor cells increased, and the hematopoietic cytokines decreased. And ARG-V promoted the transformation of myelosuppression cells from G0/G1 to S and from S to G2/M. ARG-V could up-regulate the expression of MEK and p-ERK, and low dose ARG-V is not as effective in all aspects as high dose ARG-V.

CONCLUSION

ARG-V can effectively alleviate the myelosuppression that caused by intraperitoneal injection of CTX in 100mg/kg, and ARG-V can promote the proliferation and differentiation of hematopoietic progenitor cells and improve immunity, and the effect of high-dose Arctigenin-Valine ester is more significant to some extent.

摘要

目的

探讨牛蒡苷元-缬氨酸酯(ARG-V)是否可以治疗化疗引起的骨髓抑制。

方法

采用自动血液分析仪检测小鼠外周血中白细胞的数量,体外培养造血祖细胞集落 CFU-GM、CFU-E、BFU-E 和 CFU-Meg。在倒置显微镜下计数造血祖细胞集落和骨髓单个核细胞(BMNCs)。采用 ELISA 法检测细胞因子 GM-CSF、EPO 和 TPO 的表达。采用流式细胞术测量细胞周期。采用 Western blot 定量检测相关蛋白 MEK 和 p-ERK 的表达,并定量检测胸腺指数和脾脏指数。

结果

服用 ARG-V 后,小鼠外周血白细胞逐渐恢复正常,骨髓有核细胞数量增加,胸腺指数增加,脾脏指数降低,造血祖细胞数量增加,造血细胞因子减少。ARG-V 促进骨髓抑制细胞从 G0/G1 期向 S 期和 S 期向 G2/M 期转化。ARG-V 可上调 MEK 和 p-ERK 的表达,低剂量 ARG-V 在各方面的效果不如高剂量 ARG-V。

结论

ARG-V 能有效缓解 100mg/kg 腹腔注射 CTX 引起的骨髓抑制,促进造血祖细胞的增殖和分化,提高免疫力,高剂量牛蒡苷元-缬氨酸酯的效果在一定程度上更为显著。

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