临床传统医学和药理学（英文）2025，Vol.6Issue(2)：53-65,13.DOI:10.1016/j.ctmp.2025.200213
龟鹿二仙胶调控造血干细胞p16Ink4a基因的组蛋白甲基化水平缓解化疗相关骨髓抑制
Guilu erxian glue alleviates chemotherapy-induced myelosuppression by regulating histone methylation level of p16Ink4a gene in hematopoietic stem cells
摘要
Abstract
Background:Myelosuppression is a common chemotherapy-related toxicity and hematopoietic stem cells(HSCs)senescence is the main mechanism.Guilu Erxian Glue(GEG)is an effective Chinese herbal prescription for the treatment of myelosuppression in clinical,the potential mechanism needs further investigation. Objective:To explore the protective effect of GEG on HSCs during chemotherapy-induced myelosuppression and its mechanism. Methods:Eighteen H22 hepatoma-bearing mice were divided equally into three groups:control,cisplatin(DDP),and DDP+GEG groups.Peripheral blood cell counts and bone marrow nucleated cell counts were performed.Bone marrow histopathology was assessed by hematoxylin and eosin(H&E)staining.DNA damage was assessed by γ-H2AX immunofluorescence staining.The serum containing GEG was prepared for in vitro experiments.Su-peroxide dismutase(SOD)activity,cell viability,cell cycle,and aging cells were detected in vivo and in vitro.In addition,western blot,quantitative reverse transcription polymerase chain reaction(qRT-PCR),and chromatin immunoprecipitation(CHIP)assay were applied to explore the molecular mechanism. Results:GEG administration resulted in a significant increase in peripheral blood cells and bone marrow nucle-ated cells(P＜0.01),and improved the pathological histomorphology of bone marrow.Treatment with GEG or silencing of the p16Ink4a gene enhanced the SOD activity and viability of HSCs,while reducing DDP-induced DNA damage,G2-M cell cycle arrest and senescent cell formation(P＜0.001).GEG decreased both mRNA and protein levels of p16,while increased the protein and mRNA expression levels of CDK4,CDK6,and pRb both in vivo and in vitro experiments(P＜0.05).ChIP-qPCR showed that the p16Ink4a promoter region was enriched with JMJD2 and H3K36me2/me3 protein.GEG treatment up-regulated the protein and mRNA expression levels of JMJD2 and simultaneously down-regulated H3K36me2/me3 protein levels. Conclusion:Our findings suggest that GEG exerts regulatory effects on p16Ink4a gene expression through modulat-ing the levels of H3K36 methylation.This study provides important mechanistic insights into the effects of GEG on HSCs and suggests potential therapeutic applications for GEG in myelosuppression.关键词
龟鹿二仙胶/化疗/造血干细胞衰老/骨髓抑制/组蛋白甲基化Key words
Guilu erxian glue/Chemotherapy/Hematopoietic stem cells senescence/Myelosuppression/Histone methylation引用本文复制引用
王梦蕾,姜静,王珏,赖威旨,楼招欢,林胜友,邵科钉,苏景阳,曾天旎,陆金华..龟鹿二仙胶调控造血干细胞p16Ink4a基因的组蛋白甲基化水平缓解化疗相关骨髓抑制[J].临床传统医学和药理学（英文）,2025,6(2):53-65,13.基金项目
This work was supported by the Natural Science Foundation of Zhe-jiang Province of China(No.LY24H270010),and the National Natural Science Foundation of China(No.81904197). （No.LY24H270010）
